Journal articles: 'Transcriptional Regulatory Elements'

1

Lee, Tsz Kin (Bernard), and J. M. Friedman. "Analysis ofNF1 transcriptional regulatory elements." American Journal of Medical Genetics Part A 137A, no. 2 (2005): 130–35. http://dx.doi.org/10.1002/ajmg.a.30699.

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2

Heo, Hyoung-Sam, S. June Oh, Ji Min Kim, Hyung Sik Kim, and Hae Young Chung. "TREP_DB: Transcriptional regulatory elements pattern database." Biochemical and Biophysical Research Communications 394, no. 2 (April 2010): 309–16. http://dx.doi.org/10.1016/j.bbrc.2010.02.169.

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3

Jones, L., H. Richardson, and R. Saint. "Tissue-specific regulation of cyclin E transcription during Drosophila melanogaster embryogenesis." Development 127, no. 21 (November 1, 2000): 4619–30. http://dx.doi.org/10.1242/dev.127.21.4619.

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Cyclin E is an essential regulator of S phase entry. We have previously shown that transcriptional regulation of the gene that encodes Drosophila cyclin E, DmcycE, plays an important role in the control of the G(1) to S phase transition during development. We report here the first comprehensive analysis of the transcriptional regulation of a G(1)phase cell cycle regulatory gene during embryogenesis. Analysis of deficiencies, a genomic transformant and reporter gene constructs revealed that DmcycE transcription is controlled by a large and complex cis-regulatory region containing tissue- and stage-specific components. Separate regulatory elements for transcription in epidermal cells during cell cycles 14–16, central nervous system cells and peripheral nervous system cells were found. An additional cis-regulatory element drives transcription in thoracic epidermal cells that undergo a 17th cell cycle when other epidermal cells have arrested in G(1)phase prior to terminal differentiation. The complexity of DmcycE transcriptional regulation argues against a model in which DmcycE transcription is regulated simply and solely by G(1) to S phase transcription regulators such as RB, E2F and DP. Rather, our study demonstrates that tissue-specific transcriptional regulatory mechanisms are important components of the control of cyclin E transcription and thus of cell proliferation in metazoans.

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4

Andersson, Robin, Albin Sandelin, and Charles G. Danko. "A unified architecture of transcriptional regulatory elements." Trends in Genetics 31, no. 8 (August 2015): 426–33. http://dx.doi.org/10.1016/j.tig.2015.05.007.

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Maston, Glenn A., Sara K. Evans, and Michael R. Green. "Transcriptional Regulatory Elements in the Human Genome." Annual Review of Genomics and Human Genetics 7, no. 1 (September 2006): 29–59. http://dx.doi.org/10.1146/annurev.genom.7.080505.115623.

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Yin, Wenbing, and Nancy P. Keller. "Transcriptional regulatory elements in fungal secondary metabolism." Journal of Microbiology 49, no. 3 (June 2011): 329–39. http://dx.doi.org/10.1007/s12275-011-1009-1.

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7

Rohrer, Jurg, and Mary Ellen Conley. "Transcriptional Regulatory Elements Within the First Intron of Bruton's Tyrosine Kinase." Blood 91, no. 1 (January 1, 1998): 214–21. http://dx.doi.org/10.1182/blood.v91.1.214.

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Abstract Defects in the gene for Bruton's tyrosine kinase (Btk) result in the disorder X-linked agammaglobulinemia (XLA). Whereas XLA is characterized by a profound defect in B-cell development, Btk is expressed in both the B lymphocyte and myeloid cell lineages. We evaluated a patient with XLA who had reduced amounts of Btk transcript but no abnormalities in his coding sequence. A single base-pair substitution in the first intron of Btk was identified in this patient, suggesting that this region may contain regulatory elements. Using reporter constructs we identified two transcriptional control elements in the first 500 bp of intron 1. A strong positive regulator, active in both pre-B cells and B cells, was identified within the first 43 bp of the intron. Gel-shift assays identified two Sp1 binding sites within this element. The patient's mutation results in an altered binding specificity of the proximal Sp1 binding site. A negative regulator, active in pre-B cells only, was located between base pairs 281 and 491 of the intron. These findings indicate that regulation of Btk transcription is complex and may involve several transcriptional regulatory factors at the different stages of B-cell differentiation.

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Rohrer, Jurg, and Mary Ellen Conley. "Transcriptional Regulatory Elements Within the First Intron of Bruton's Tyrosine Kinase." Blood 91, no. 1 (January 1, 1998): 214–21. http://dx.doi.org/10.1182/blood.v91.1.214.214_214_221.

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Defects in the gene for Bruton's tyrosine kinase (Btk) result in the disorder X-linked agammaglobulinemia (XLA). Whereas XLA is characterized by a profound defect in B-cell development, Btk is expressed in both the B lymphocyte and myeloid cell lineages. We evaluated a patient with XLA who had reduced amounts of Btk transcript but no abnormalities in his coding sequence. A single base-pair substitution in the first intron of Btk was identified in this patient, suggesting that this region may contain regulatory elements. Using reporter constructs we identified two transcriptional control elements in the first 500 bp of intron 1. A strong positive regulator, active in both pre-B cells and B cells, was identified within the first 43 bp of the intron. Gel-shift assays identified two Sp1 binding sites within this element. The patient's mutation results in an altered binding specificity of the proximal Sp1 binding site. A negative regulator, active in pre-B cells only, was located between base pairs 281 and 491 of the intron. These findings indicate that regulation of Btk transcription is complex and may involve several transcriptional regulatory factors at the different stages of B-cell differentiation.

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9

Chávez, Joselyn, Damien P. Devos, and Enrique Merino. "Complementary Tendencies in the Use of Regulatory Elements (Transcription Factors, Sigma Factors, and Riboswitches) in Bacteria and Archaea." Journal of Bacteriology 203, no. 2 (October 19, 2020): e00413-20. http://dx.doi.org/10.1128/jb.00413-20.

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ABSTRACTIn prokaryotes, the key players in transcription initiation are sigma factors and transcription factors that bind to DNA to modulate the process, while premature transcription termination at the 5′ end of the genes is regulated by attenuation and, in particular, by attenuation associated with riboswitches. In this study, we describe the distribution of these regulators across phylogenetic groups of bacteria and archaea and find that their abundance not only depends on the genome size, as previously described, but also varies according to the phylogeny of the organism. Furthermore, we observed a tendency for organisms to compensate for the low frequencies of a particular type of regulatory element (i.e., transcription factors) with a high frequency of other types of regulatory elements (i.e., sigma factors). This study provides a comprehensive description of the more abundant COG, KEGG, and Rfam families of transcriptional regulators present in prokaryotic genomes.IMPORTANCE In this study, we analyzed the relationship between the relative frequencies of the primary regulatory elements in bacteria and archaea, namely, transcription factors, sigma factors, and riboswitches. In bacteria, we reveal a compensatory behavior for transcription factors and sigma factors, meaning that in phylogenetic groups in which the relative number of transcription factors was low, we found a tendency for the number of sigma factors to be high and vice versa. For most of the phylogenetic groups analyzed here, except for Firmicutes and Tenericutes, a clear relationship with other mechanisms was not detected for transcriptional riboswitches, suggesting that their low frequency in most genomes does not constitute a significant impact on the global variety of transcriptional regulatory elements in prokaryotic organisms.

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10

Iñiguez-Lluhí, Jorge A., and David Pearce. "A Common Motif within the Negative Regulatory Regions of Multiple Factors Inhibits Their Transcriptional Synergy." Molecular and Cellular Biology 20, no. 16 (August 15, 2000): 6040–50. http://dx.doi.org/10.1128/mcb.20.16.6040-6050.2000.

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ABSTRACT DNA regulatory elements frequently harbor multiple recognition sites for several transcriptional activators. The response mounted from such compound response elements is often more pronounced than the simple sum of effects observed at single binding sites. The determinants of such transcriptional synergy and its control, however, are poorly understood. Through a genetic approach, we have uncovered a novel protein motif that limits the transcriptional synergy of multiple DNA-binding regulators. Disruption of these conserved synergy control motifs (SC motifs) selectively increases activity at compound, but not single, response elements. Although isolated SC motifs do not regulate transcription when tethered to DNA, their transfer to an activator lacking them is sufficient to impose limits on synergy. Mechanistic analysis of the two SC motifs found in the glucocorticoid receptor N-terminal region reveals that they function irrespective of the arrangement of the receptor binding sites or their distance from the transcription start site. Proper function, however, requires the receptor's ligand-binding domain and an engaged dimer interface. Notably, the motifs are not functional in yeast and do not alter the effect of p160 coactivators, suggesting that they require other nonconserved components to operate. Many activators across multiple classes harbor seemingly unrelated negative regulatory regions. The presence of SC motifs within them, however, suggests a common function and identifies SC motifs as critical elements of a general mechanism to modulate higher-order interactions among transcriptional regulators.

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11

Perez-Albuerne, E. D., G. Schatteman, L. K. Sanders, and D. Nathans. "Transcriptional regulatory elements downstream of the JunB gene." Proceedings of the National Academy of Sciences 90, no. 24 (December 15, 1993): 11960–64. http://dx.doi.org/10.1073/pnas.90.24.11960.

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12

Perales, Mariano, Kevin Rodriguez, Stephen Snipes, Ram Kishor Yadav, Mercedes Diaz-Mendoza, and G. Venugopala Reddy. "Threshold-dependent transcriptional discrimination underlies stem cell homeostasis." Proceedings of the National Academy of Sciences 113, no. 41 (September 26, 2016): E6298—E6306. http://dx.doi.org/10.1073/pnas.1607669113.

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Transcriptional mechanisms that underlie the dose-dependent regulation of gene expression in animal development have been studied extensively. However, the mechanisms of dose-dependent transcriptional regulation in plant development have not been understood. In Arabidopsis shoot apical meristems, WUSCHEL (WUS), a stem cell-promoting transcription factor, accumulates at a higher level in the rib meristem and at a lower level in the central zone where it activates its own negative regulator, CLAVATA3 (CLV3). How WUS regulates CLV3 levels has not been understood. Here we show that WUS binds a group of cis-elements, cis- regulatory module, in the CLV3-regulatory region, with different affinities and conformations, consisting of monomers at lower concentration and as dimers at a higher level. By deleting cis elements, manipulating the WUS-binding affinity and the homodimerization threshold of cis elements, and manipulating WUS levels, we show that the same cis elements mediate both the activation and repression of CLV3 at lower and higher WUS levels, respectively. The concentration-dependent transcriptional discrimination provides a mechanistic framework to explain the regulation of CLV3 levels that is critical for stem cell homeostasis.

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13

Yutzey, K. E., R. L. Kline, and S. F. Konieczny. "An internal regulatory element controls troponin I gene expression." Molecular and Cellular Biology 9, no. 4 (April 1989): 1397–405. http://dx.doi.org/10.1128/mcb.9.4.1397.

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During skeletal myogenesis, approximately 20 contractile proteins and related gene products temporally accumulate as the cells fuse to form multinucleated muscle fibers. In most instances, the contractile protein genes are regulated transcriptionally, which suggests that a common molecular mechanism may coordinate the expression of this diverse and evolutionarily unrelated gene set. Recent studies have examined the muscle-specific cis-acting elements associated with numerous contractile protein genes. All of the identified regulatory elements are positioned in the 5'-flanking regions, usually within 1,500 base pairs of the transcription start site. Surprisingly, a DNA consensus sequence that is common to each contractile protein gene has not been identified. In contrast to the results of these earlier studies, we have found that the 5'-flanking region of the quail troponin I (TnI) gene is not sufficient to permit the normal myofiber transcriptional activation of the gene. Instead, the TnI gene utilizes a unique internal regulatory element that is responsible for the correct myofiber-specific expression pattern associated with the TnI gene. This is the first example in which a contractile protein gene has been shown to rely primarily on an internal regulatory element to elicit transcriptional activation during myogenesis. The diversity of regulatory elements associated with the contractile protein genes suggests that the temporal expression of the genes may involve individual cis-trans regulatory components specific for each gene.

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14

Yutzey, K. E., R. L. Kline, and S. F. Konieczny. "An internal regulatory element controls troponin I gene expression." Molecular and Cellular Biology 9, no. 4 (April 1989): 1397–405. http://dx.doi.org/10.1128/mcb.9.4.1397-1405.1989.

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During skeletal myogenesis, approximately 20 contractile proteins and related gene products temporally accumulate as the cells fuse to form multinucleated muscle fibers. In most instances, the contractile protein genes are regulated transcriptionally, which suggests that a common molecular mechanism may coordinate the expression of this diverse and evolutionarily unrelated gene set. Recent studies have examined the muscle-specific cis-acting elements associated with numerous contractile protein genes. All of the identified regulatory elements are positioned in the 5'-flanking regions, usually within 1,500 base pairs of the transcription start site. Surprisingly, a DNA consensus sequence that is common to each contractile protein gene has not been identified. In contrast to the results of these earlier studies, we have found that the 5'-flanking region of the quail troponin I (TnI) gene is not sufficient to permit the normal myofiber transcriptional activation of the gene. Instead, the TnI gene utilizes a unique internal regulatory element that is responsible for the correct myofiber-specific expression pattern associated with the TnI gene. This is the first example in which a contractile protein gene has been shown to rely primarily on an internal regulatory element to elicit transcriptional activation during myogenesis. The diversity of regulatory elements associated with the contractile protein genes suggests that the temporal expression of the genes may involve individual cis-trans regulatory components specific for each gene.

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15

Cai, Yao-Min, Kalyani Kallam, Henry Tidd, Giovanni Gendarini, Amanda Salzman, and Nicola J. Patron. "Rational design of minimal synthetic promoters for plants." Nucleic Acids Research 48, no. 21 (August 28, 2020): 11845–56. http://dx.doi.org/10.1093/nar/gkaa682.

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Abstract Promoters serve a critical role in establishing baseline transcriptional capacity through the recruitment of proteins, including transcription factors. Previously, a paucity of data for cis-regulatory elements in plants meant that it was challenging to determine which sequence elements in plant promoter sequences contributed to transcriptional function. In this study, we have identified functional elements in the promoters of plant genes and plant pathogens that utilize plant transcriptional machinery for gene expression. We have established a quantitative experimental system to investigate transcriptional function, investigating how identity, density and position contribute to regulatory function. We then identified permissive architectures for minimal synthetic plant promoters enabling the computational design of a suite of synthetic promoters of different strengths. These have been used to regulate the relative expression of output genes in simple genetic devices.

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16

Khan, Arshad H., Andy Lin, and Desmond J. Smith. "Discovery and Characterization of Human Exonic Transcriptional Regulatory Elements." PLoS ONE 7, no. 9 (September 24, 2012): e46098. http://dx.doi.org/10.1371/journal.pone.0046098.

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17

Xu, Zhi-Li, Hiroyuki Mizuguchi, Akiko Ishii-Watabe, Eriko Uchida, Tadanori Mayumi, and Takao Hayakawa. "Optimization of transcriptional regulatory elements for constructing plasmid vectors." Gene 272, no. 1-2 (July 2001): 149–56. http://dx.doi.org/10.1016/s0378-1119(01)00550-9.

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18

Budden, David M., Daniel G. Hurley, and Edmund J. Crampin. "Predictive modelling of gene expression from transcriptional regulatory elements." Briefings in Bioinformatics 16, no. 4 (September 16, 2014): 616–28. http://dx.doi.org/10.1093/bib/bbu034.

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19

Rogers, Eric D., Jenniffer R. Ramalie, Erin N. McMurray, and Jennifer V. Schmidt. "Localizing Transcriptional Regulatory Elements at the Mouse Dlk1 Locus." PLoS ONE 7, no. 5 (May 11, 2012): e36483. http://dx.doi.org/10.1371/journal.pone.0036483.

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20

GuhaThakurta, D. "Computational identification of transcriptional regulatory elements in DNA sequence." Nucleic Acids Research 34, no. 12 (July 19, 2006): 3585–98. http://dx.doi.org/10.1093/nar/gkl372.

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21

Xiong, Yun, Guangyong Zheng, Qing Yang, and Yangyong Zhu. "A Collaborative Multiagent System for Mining Transcriptional Regulatory Elements." IEEE Intelligent Systems 24, no. 3 (May 2009): 26–37. http://dx.doi.org/10.1109/mis.2009.40.

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22

Thomas, Amarni L., Judith Marsman, Jisha Antony, William Schierding, Justin M. O’Sullivan, and Julia A. Horsfield. "Transcriptional Regulation of RUNX1: An Informatics Analysis." Genes 12, no. 8 (July 29, 2021): 1175. http://dx.doi.org/10.3390/genes12081175.

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The RUNX1/AML1 gene encodes a developmental transcription factor that is an important regulator of haematopoiesis in vertebrates. Genetic disruptions to the RUNX1 gene are frequently associated with acute myeloid leukaemia. Gene regulatory elements (REs), such as enhancers located in non-coding DNA, are likely to be important for Runx1 transcription. Non-coding elements that modulate Runx1 expression have been investigated over several decades, but how and when these REs function remains poorly understood. Here we used bioinformatic methods and functional data to characterise the regulatory landscape of vertebrate Runx1. We identified REs that are conserved between human and mouse, many of which produce enhancer RNAs in diverse tissues. Genome-wide association studies detected single nucleotide polymorphisms in REs, some of which correlate with gene expression quantitative trait loci in tissues in which the RE is active. Our analyses also suggest that REs can be variant in haematological malignancies. In summary, our analysis identifies features of the RUNX1 regulatory landscape that are likely to be important for the regulation of this gene in normal and malignant haematopoiesis.

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Li, Youlin, Yutaka Okuno, Pu Zhang, Hanna S. Radomska, Hui-min Chen, Hiromi Iwasaki, Koichi Akashi, et al. "Regulation of the PU.1 gene by distal elements." Blood 98, no. 10 (November 15, 2001): 2958–65. http://dx.doi.org/10.1182/blood.v98.10.2958.

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Abstract The transcription factor PU.1 (also known as Spi-1) plays a critical role in the development of the myeloid lineages, and myeloid cells derived from PU.1−/− animals are blocked at the earliest stage of myeloid differentiation. Expression of the PU.1 gene is tightly regulated during normal hematopoietic development, and dysregulation of PU.1 expression can lead to erythroleukemia. However, relatively little is known about how the PU.1 gene is regulated in vivo. Here it is shown that myeloid cell type–specific expression of PU.1 in stable cell lines and transgenic animals is conferred by a 91-kilobase (kb) murine genomic DNA fragment that consists of the entire PU.1 gene (20 kb) plus approximately 35 kb of upstream and downstream sequences, respectively. To further map the important transcriptional regulatory elements, deoxyribonuclease I hypersensitive site mapping studies revealed at least 3 clusters in the PU.1 gene. A 3.5-kb fragment containing one of these deoxyribonuclease I hypersensitive sites, located −14 kb 5′ of the transcriptional start site, conferred myeloid cell type–specific expression in stably transfected cell lines, suggesting that within this region is an element important for myeloid specific expression of PU.1. Further analysis of this myeloid-specific regulatory element will provide insight into the regulation of this key transcriptional regulator and may be useful as a tool for targeting expression to the myeloid lineage.

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Xiao, Gaoping, Jianxin He, and Laurence G. Rahme. "Mutation analysis of the Pseudomonas aeruginosa mvfR and pqsABCDE gene promoters demonstrates complex quorum-sensing circuitry." Microbiology 152, no. 6 (June 1, 2006): 1679–86. http://dx.doi.org/10.1099/mic.0.28605-0.

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The LysR-type transcriptional regulator MvfR (PqsR) (multiple virulence factor regulator) plays a critical role in Pseudomonas aeruginosa pathogenicity via the transcriptional regulation of multiple quorum-sensing (QS)-regulated virulence factors. LasR activates full mvfR transcription, and MvfR subsequently activates pqsA–E expression. This study identifies and characterizes the key cis-regulatory elements through which mvfR and pqsA–E transcription is regulated in the highly virulent P. aeruginosa strain PA14. Deletion and site-directed mutagenesis indicate that: (1) LasR activates mvfR transcription by binding to a las/rhl box, CTAACAAAAGACATAG, centred at −513 bp upstream of the MvfR translational start site; and (2) RhlR represses pqsA transcription by binding to a las/rhl box, CTGTGAGATTTGGGAG, centred at −311 bp upstream of the pqsA transcriptional initiation site. Furthermore, it is shown that MvfR activates pqsA–E transcription by binding to a LysR box, TTCGGACTCCGAA, centred at −45 bp relative to the pqsA transcriptional initiation site, demonstrating that this LysR box has a critical role in the physical interaction between the MvfR protein and the pqsA promoter. These results provide new insights into the regulatory relationships between LasR and mvfR, and between MvfR/RhlR and the pqs operon, and elucidate further the complex regulation of the P. aeruginosa QS circuitry.

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25

Topper, J. N., and D. A. Clayton. "Identification of transcriptional regulatory elements in human mitochondrial DNA by linker substitution analysis." Molecular and Cellular Biology 9, no. 3 (March 1989): 1200–1211. http://dx.doi.org/10.1128/mcb.9.3.1200.

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Human mitochondrial DNA contains two major promoters, one for transcription of each strand of the helix. Previous mapping and mutagenesis data have localized these regulatory elements and have suggested regions important to their function. In order to define, at high resolution, the sequences critical for accurate and efficient transcriptional initiation, a linker substitution analysis of the entire promoter region was performed. Each promoter was shown to consist of approximately 50 base pairs comprising two functionally distinct elements. These and previous data strongly support a mode of transcription initiation requiring minimal sequences surrounding the initiation sites that are likely interactive with core polymerase and upstream regulatory domains capable of binding a transcription factor that modulates the efficiency of transcription initiation. Furthermore, in at least one case, this upstream regulatory domain is capable of operating bidirectionally.

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Topper, J. N., and D. A. Clayton. "Identification of transcriptional regulatory elements in human mitochondrial DNA by linker substitution analysis." Molecular and Cellular Biology 9, no. 3 (March 1989): 1200–1211. http://dx.doi.org/10.1128/mcb.9.3.1200-1211.1989.

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Human mitochondrial DNA contains two major promoters, one for transcription of each strand of the helix. Previous mapping and mutagenesis data have localized these regulatory elements and have suggested regions important to their function. In order to define, at high resolution, the sequences critical for accurate and efficient transcriptional initiation, a linker substitution analysis of the entire promoter region was performed. Each promoter was shown to consist of approximately 50 base pairs comprising two functionally distinct elements. These and previous data strongly support a mode of transcription initiation requiring minimal sequences surrounding the initiation sites that are likely interactive with core polymerase and upstream regulatory domains capable of binding a transcription factor that modulates the efficiency of transcription initiation. Furthermore, in at least one case, this upstream regulatory domain is capable of operating bidirectionally.

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Ling, Guoyu, Aarathi Sugathan, Tali Mazor, Ernest Fraenkel, and David J. Waxman. "Unbiased, Genome-Wide In Vivo Mapping of Transcriptional Regulatory Elements Reveals Sex Differences in Chromatin Structure Associated with Sex-Specific Liver Gene Expression." Molecular and Cellular Biology 30, no. 23 (September 27, 2010): 5531–44. http://dx.doi.org/10.1128/mcb.00601-10.

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ABSTRACT We have used a simple and efficient method to identify condition-specific transcriptional regulatory sites in vivo to help elucidate the molecular basis of sex-related differences in transcription, which are widespread in mammalian tissues and affect normal physiology, drug response, inflammation, and disease. To systematically uncover transcriptional regulators responsible for these differences, we used DNase hypersensitivity analysis coupled with high-throughput sequencing to produce condition-specific maps of regulatory sites in male and female mouse livers and in livers of male mice feminized by continuous infusion of growth hormone (GH). We identified 71,264 hypersensitive sites, with 1,284 showing robust sex-related differences. Continuous GH infusion suppressed the vast majority of male-specific sites and induced a subset of female-specific sites in male livers. We also identified broad genomic regions (up to ∼100 kb) showing sex-dependent hypersensitivity and similar patterns of GH responses. We found a strong association of sex-specific sites with sex-specific transcription; however, a majority of sex-specific sites were >100 kb from sex-specific genes. By analyzing sequence motifs within regulatory regions, we identified two known regulators of liver sexual dimorphism and several new candidates for further investigation. This approach can readily be applied to mapping condition-specific regulatory sites in mammalian tissues under a wide variety of physiological conditions.

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Qiu, Yichun, and Claudia Köhler. "Mobility connects: transposable elements wire new transcriptional networks by transferring transcription factor binding motifs." Biochemical Society Transactions 48, no. 3 (June 23, 2020): 1005–17. http://dx.doi.org/10.1042/bst20190937.

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Transposable elements (TEs) constitute major fractions of plant genomes. Their potential to be mobile provides them with the capacity to cause major genome rearrangements. Those effects are potentially deleterious and enforced the evolution of epigenetic suppressive mechanisms controlling TE activity. However, beyond their deleterious effects, TE insertions can be neutral or even advantageous for the host, leading to long-term retention of TEs in the host genome. Indeed, TEs are increasingly recognized as major drivers of evolutionary novelties by regulating the expression of nearby genes. TEs frequently contain binding motifs for transcription factors and capture binding motifs during transposition, which they spread through the genome by transposition. Thus, TEs drive the evolution and diversification of gene regulatory networks by recruiting lineage-specific targets under the regulatory control of specific transcription factors. This process can explain the rapid and repeated evolution of developmental novelties, such as C4 photosynthesis and a wide spectrum of stress responses in plants. It also underpins the convergent evolution of embryo nourishing tissues, the placenta in mammals and the endosperm in flowering plants. Furthermore, the gene regulatory network underlying flower development has also been largely reshaped by TE-mediated recruitment of regulatory elements; some of them being preserved across long evolutionary timescales. In this review, we highlight the potential role of TEs as evolutionary toolkits in plants by showcasing examples of TE-mediated evolutionary novelties.

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Braikia, Fatima-Zohra, Caroline Conte, Mohamed Moutahir, Yves Denizot, Michel Cogné, and Ahmed Amine Khamlichi. "Developmental Switch in the Transcriptional Activity of a Long-Range Regulatory Element." Molecular and Cellular Biology 35, no. 19 (July 20, 2015): 3370–80. http://dx.doi.org/10.1128/mcb.00509-15.

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Eukaryotic gene expression is often controlled by distant regulatory elements. In developing B lymphocytes, transcription is associated with V(D)J recombination at immunoglobulin loci. This process is regulated by remotecis-acting elements. At the immunoglobulin heavy chain (IgH) locus, the 3′ regulatory region (3′RR) promotes transcription in mature B cells. This led to the notion that the 3′RR orchestrates theIgHlocus activity at late stages of B cell maturation only. However, long-range interactions involving the 3′RR were detected in early B cells, but the functional consequences of these interactions were unknown. Here we show that not only does the 3′RR affect transcription at distant sites within theIgHvariable region but also it conveys a transcriptional silencing activity on both sense and antisense transcription. The 3′RR-mediated silencing activity is switched off upon completion of VH-DJHrecombination. Our findings reveal a developmentally controlled, stage-dependent shift in the transcriptional activity of a master regulatory element.

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Godbout, R., R. Ingram, and S. M. Tilghman. "Multiple regulatory elements in the intergenic region between the alpha-fetoprotein and albumin genes." Molecular and Cellular Biology 6, no. 2 (February 1986): 477–87. http://dx.doi.org/10.1128/mcb.6.2.477.

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Three enhancer elements spanning a distance of 7 kilobases have been found at the 5' end of the alpha-fetoprotein (AFP) gene. These elements were identified by transient expression assay after the introduction of a modified mouse AFP gene with variable amounts of 5' flanking sequence into a human hepatoma cell line, Hep G2. These regulatory elements function in a position-independent and orientation-independent manner that is typical of enhancers. All three elements will stimulate transcription from the promoter of the herpes simplex virus thymidine kinase gene. In Hep G2 cells, transcriptional activation from the heterologous promoter was approximately 25- to 50-fold higher than the basal levels obtained in the absence of AFP enhancer elements. In HeLa cells, the increase in thymidine kinase gene transcription varied from 6- to 14-fold, indicating that the enhancer elements exhibit some cell type specificity. Deletion analysis of the region proximal to the AFP transcription initiation site identified an essential region between 85 and 52 bases upstream of the site of initiation of transcription whose removal resulted in almost complete extinction of transcriptional activity. This region, which has been shown to be dispensable for transcription in HeLa cells, defines a second tissue-specific regulatory region in the gene.

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31

Godbout, R., R. Ingram, and S. M. Tilghman. "Multiple regulatory elements in the intergenic region between the alpha-fetoprotein and albumin genes." Molecular and Cellular Biology 6, no. 2 (February 1986): 477–87. http://dx.doi.org/10.1128/mcb.6.2.477-487.1986.

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Three enhancer elements spanning a distance of 7 kilobases have been found at the 5' end of the alpha-fetoprotein (AFP) gene. These elements were identified by transient expression assay after the introduction of a modified mouse AFP gene with variable amounts of 5' flanking sequence into a human hepatoma cell line, Hep G2. These regulatory elements function in a position-independent and orientation-independent manner that is typical of enhancers. All three elements will stimulate transcription from the promoter of the herpes simplex virus thymidine kinase gene. In Hep G2 cells, transcriptional activation from the heterologous promoter was approximately 25- to 50-fold higher than the basal levels obtained in the absence of AFP enhancer elements. In HeLa cells, the increase in thymidine kinase gene transcription varied from 6- to 14-fold, indicating that the enhancer elements exhibit some cell type specificity. Deletion analysis of the region proximal to the AFP transcription initiation site identified an essential region between 85 and 52 bases upstream of the site of initiation of transcription whose removal resulted in almost complete extinction of transcriptional activity. This region, which has been shown to be dispensable for transcription in HeLa cells, defines a second tissue-specific regulatory region in the gene.

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32

Zhang, Ting, Anqi Wu, Yaping Yue, and Yu Zhao. "uORFs: Important Cis-Regulatory Elements in Plants." International Journal of Molecular Sciences 21, no. 17 (August 28, 2020): 6238. http://dx.doi.org/10.3390/ijms21176238.

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Gene expression is regulated at many levels, including mRNA transcription, translation, and post-translational modification. Compared with transcriptional regulation, mRNA translational control is a more critical step in gene expression and allows for more rapid changes of encoded protein concentrations in cells. Translation is highly regulated by complex interactions between cis-acting elements and trans-acting factors. Initiation is not only the first phase of translation, but also the core of translational regulation, because it limits the rate of protein synthesis. As potent cis-regulatory elements in eukaryotic mRNAs, upstream open reading frames (uORFs) generally inhibit the translation initiation of downstream major ORFs (mORFs) through ribosome stalling. During the past few years, with the development of RNA-seq and ribosome profiling, functional uORFs have been identified and characterized in many organisms. Here, we review uORF identification, uORF classification, and uORF-mediated translation initiation. More importantly, we summarize the translational regulation of uORFs in plant metabolic pathways, morphogenesis, disease resistance, and nutrient absorption, which open up an avenue for precisely modulating the plant growth and development, as well as environmental adaption. Additionally, we also discuss prospective applications of uORFs in plant breeding.

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Vermunt, Marit W., Di Zhang, and Gerd A. Blobel. "The interdependence of gene-regulatory elements and the 3D genome." Journal of Cell Biology 218, no. 1 (November 15, 2018): 12–26. http://dx.doi.org/10.1083/jcb.201809040.

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Imaging studies, high-resolution chromatin conformation maps, and genome-wide occupancy data of architectural proteins have revealed that genome topology is tightly intertwined with gene expression. Cross-talk between gene-regulatory elements is often organized within insulated neighborhoods, and regulatory cues that induce transcriptional changes can reshape chromatin folding patterns and gene positioning within the nucleus. The cause–consequence relationship of genome architecture and gene expression is intricate, and its molecular mechanisms are under intense investigation. Here, we review the interdependency of transcription and genome organization with emphasis on enhancer–promoter contacts in gene regulation.

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Duren, Zhana, Xi Chen, Rui Jiang, Yong Wang, and Wing Hung Wong. "Modeling gene regulation from paired expression and chromatin accessibility data." Proceedings of the National Academy of Sciences 114, no. 25 (June 2, 2017): E4914—E4923. http://dx.doi.org/10.1073/pnas.1704553114.

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The rapid increase of genome-wide datasets on gene expression, chromatin states, and transcription factor (TF) binding locations offers an exciting opportunity to interpret the information encoded in genomes and epigenomes. This task can be challenging as it requires joint modeling of context-specific activation of cis-regulatory elements (REs) and the effects on transcription of associated regulatory factors. To meet this challenge, we propose a statistical approach based on paired expression and chromatin accessibility (PECA) data across diverse cellular contexts. In our approach, we model (i) the localization to REs of chromatin regulators (CRs) based on their interaction with sequence-specific TFs, (ii) the activation of REs due to CRs that are localized to them, and (iii) the effect of TFs bound to activated REs on the transcription of target genes (TGs). The transcriptional regulatory network inferred by PECA provides a detailed view of how trans- and cis-regulatory elements work together to affect gene expression in a context-specific manner. We illustrate the feasibility of this approach by analyzing paired expression and accessibility data from the mouse Encyclopedia of DNA Elements (ENCODE) and explore various applications of the resulting model.

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Wakabayashi, Aoi, Jacob C. Ulirsch, Leif S. Ludwig, Claudia Fiorini, Makiko Yasuda, Avik Choudhuri, Patrick McDonel, Leonard I. Zon, and Vijay G. Sankaran. "Insight into GATA1 transcriptional activity through interrogation of cis elements disrupted in human erythroid disorders." Proceedings of the National Academy of Sciences 113, no. 16 (April 4, 2016): 4434–39. http://dx.doi.org/10.1073/pnas.1521754113.

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Whole-exome sequencing has been incredibly successful in identifying causal genetic variants and has revealed a number of novel genes associated with blood and other diseases. One limitation of this approach is that it overlooks mutations in noncoding regulatory elements. Furthermore, the mechanisms by which mutations in transcriptional cis-regulatory elements result in disease remain poorly understood. Here we used CRISPR/Cas9 genome editing to interrogate three such elements harboring mutations in human erythroid disorders, which in all cases are predicted to disrupt a canonical binding motif for the hematopoietic transcription factor GATA1. Deletions of as few as two to four nucleotides resulted in a substantial decrease (>80%) in target gene expression. Isolated deletions of the canonical GATA1 binding motif completely abrogated binding of the cofactor TAL1, which binds to a separate motif. Having verified the functionality of these three GATA1 motifs, we demonstrate strong evolutionary conservation of GATA1 motifs in regulatory elements proximal to other genes implicated in erythroid disorders, and show that targeted disruption of such elements results in altered gene expression. By modeling transcription factor binding patterns, we show that multiple transcription factors are associated with erythroid gene expression, and have created predictive maps modeling putative disruptions of their binding sites at key regulatory elements. Our study provides insight into GATA1 transcriptional activity and may prove a useful resource for investigating the pathogenicity of noncoding variants in human erythroid disorders.

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Pintus, Sergey S., Ilya R. Akberdin, Ivan Yevshin, Pavel Makhnovskii, Oksana Tyapkina, Islam Nigmetzyanov, Leniz Nurullin, et al. "Genome-Wide Atlas of Promoter Expression Reveals Contribution of Transcribed Regulatory Elements to Genetic Control of Disuse-Mediated Atrophy of Skeletal Muscle." Biology 10, no. 6 (June 20, 2021): 557. http://dx.doi.org/10.3390/biology10060557.

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The prevention of muscle atrophy carries with it clinical significance for the control of increased morbidity and mortality following physical inactivity. While major transcriptional events associated with muscle atrophy-recovery processes are the subject of active research on the gene level, the contribution of non-coding regulatory elements and alternative promoter usage is a major source for both the production of alternative protein products and new insights into the activity of transcription factors. We used the cap-analysis of gene expression (CAGE) to create a genome-wide atlas of promoter-level transcription in fast (m. EDL) and slow (m. soleus) muscles in rats that were subjected to hindlimb unloading and subsequent recovery. We found that the genetic regulation of the atrophy-recovery cycle in two types of muscle is mediated by different pathways, including a unique set of non-coding transcribed regulatory elements. We showed that the activation of “shadow” enhancers is tightly linked to specific stages of atrophy and recovery dynamics, with the largest number of specific regulatory elements being transcriptionally active in the muscles on the first day of recovery after a week of disuse. The developed comprehensive database of transcription of regulatory elements will further stimulate research on the gene regulation of muscle homeostasis in mammals.

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Hampsey, Michael. "Molecular Genetics of the RNA Polymerase II General Transcriptional Machinery." Microbiology and Molecular Biology Reviews 62, no. 2 (June 1, 1998): 465–503. http://dx.doi.org/10.1128/mmbr.62.2.465-503.1998.

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SUMMARY Transcription initiation by RNA polymerase II (RNA pol II) requires interaction between cis-acting promoter elements and trans-acting factors. The eukaryotic promoter consists of core elements, which include the TATA box and other DNA sequences that define transcription start sites, and regulatory elements, which either enhance or repress transcription in a gene-specific manner. The core promoter is the site for assembly of the transcription preinitiation complex, which includes RNA pol II and the general transcription fctors TBP, TFIIB, TFIIE, TFIIF, and TFIIH. Regulatory elements bind gene-specific factors, which affect the rate of transcription by interacting, either directly or indirectly, with components of the general transcriptional machinery. A third class of transcription factors, termed coactivators, is not required for basal transcription in vitro but often mediates activation by a broad spectrum of activators. Accordingly, coactivators are neither gene-specific nor general transcription factors, although gene-specific coactivators have been described in metazoan systems. Transcriptional repressors include both gene-specific and general factors. Similar to coactivators, general transcriptional repressors affect the expression of a broad spectrum of genes yet do not repress all genes. General repressors either act through the core transcriptional machinery or are histone related and presumably affect chromatin function. This review focuses on the global effectors of RNA polymerase II transcription in yeast, including the general transcription factors, the coactivators, and the general repressors. Emphasis is placed on the role that yeast genetics has played in identifying these factors and their associated functions.

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Toenhake, Christa G., and Richárd Bártfai. "What functional genomics has taught us about transcriptional regulation in malaria parasites." Briefings in Functional Genomics 18, no. 5 (April 26, 2019): 290–301. http://dx.doi.org/10.1093/bfgp/elz004.

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Abstract Malaria parasites are characterized by a complex life cycle that is accompanied by dynamic gene expression patterns. The factors and mechanisms that regulate gene expression in these parasites have been searched for even before the advent of next generation sequencing technologies. Functional genomics approaches have substantially boosted this area of research and have yielded significant insights into the interplay between epigenetic, transcriptional and post-transcriptional mechanisms. Recently, considerable progress has been made in identifying sequence-specific transcription factors and DNA-encoded regulatory elements. Here, we review the insights obtained from these efforts including the characterization of core promoters, the involvement of sequence-specific transcription factors in life cycle progression and the mapping of gene regulatory elements. Furthermore, we discuss recent developments in the field of functional genomics and how they might contribute to further characterization of this complex gene regulatory network.

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Göttgens, Berthold, Rita Ferreira, Maria-José Sanchez, Shoko Ishibashi, Juan Li, Dominik Spensberger, Pascal Lefevre, et al. "cis-Regulatory Remodeling of the SCL Locus during Vertebrate Evolution." Molecular and Cellular Biology 30, no. 24 (October 18, 2010): 5741–51. http://dx.doi.org/10.1128/mcb.00870-10.

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ABSTRACT Development progresses through a sequence of cellular identities which are determined by the activities of networks of transcription factor genes. Alterations in cis-regulatory elements of these genes play a major role in evolutionary change, but little is known about the mechanisms responsible for maintaining conserved patterns of gene expression. We have studied the evolution of cis-regulatory mechanisms controlling the SCL gene, which encodes a key transcriptional regulator of blood, vasculature, and brain development and exhibits conserved function and pattern of expression throughout vertebrate evolution. SCL cis-regulatory elements are conserved between frog and chicken but accrued alterations at an accelerated rate between 310 and 200 million years ago, with subsequent fixation of a new cis-regulatory pattern at the beginning of the mammalian radiation. As a consequence, orthologous elements shared by mammals and lower vertebrates exhibit functional differences and binding site turnover between widely separated cis-regulatory modules. However, the net effect of these alterations is constancy of overall regulatory inputs and of expression pattern. Our data demonstrate remarkable cis-regulatory remodelling across the SCL locus and indicate that stable patterns of expression can mask extensive regulatory change. These insights illuminate our understanding of vertebrate evolution.

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Hill, Robert E., and Laura A. Lettice. "Alterations to the remote control of Shh gene expression cause congenital abnormalities." Philosophical Transactions of the Royal Society B: Biological Sciences 368, no. 1620 (June 19, 2013): 20120357. http://dx.doi.org/10.1098/rstb.2012.0357.

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Multi-species conserved non-coding elements occur in the vertebrate genome and are clustered in the vicinity of developmentally regulated genes. Many are known to act as cis -regulators of transcription and may reside at long distances from the genes they regulate. However, the relationship of conserved sequence to encoded regulatory information and indeed, the mechanism by which these contribute to long-range transcriptional regulation is not well understood. The ZRS, a highly conserved cis -regulator, is a paradigm for such long-range gene regulation. The ZRS acts over approximately 1 Mb to control spatio-temporal expression of Shh in the limb bud and mutations within it result in a number of limb abnormalities, including polydactyly, tibial hypoplasia and syndactyly. We describe the activity of this developmental regulator and discuss a number of mechanisms by which regulatory mutations in this enhancer function to cause congenital abnormalities.

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OGBOURNE, Steven, and Toni M. ANTALIS. "Transcriptional control and the role of silencers in transcriptional regulation in eukaryotes." Biochemical Journal 331, no. 1 (April 1, 1998): 1–14. http://dx.doi.org/10.1042/bj3310001.

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Mechanisms controlling transcription and its regulation are fundamental to our understanding of molecular biology and, ultimately, cellular biology. Our knowledge of transcription initiation and integral factors such as RNA polymerase is considerable, and more recently our understanding of the involvement of enhancers and complexes such as holoenzyme and mediator has increased dramatically. However, an understanding of transcriptional repression is also essential for a complete understanding of promoter structure and the regulation of gene expression. Transcriptional repression in eukaryotes is achieved through ‘silencers ’, of which there are two types, namely ‘silencer elements ’ and ‘negative regulatory elements ’ (NREs). Silencer elements are classical, position-independent elements that direct an active repression mechanism, and NREs are position-dependent elements that direct a passive repression mechanism. In addition, ‘repressors ’ are DNA-binding trasncription factors that interact directly with silencers. A review of the recent literature reveals that it is the silencer itself and its context within a given promoter, rather than the interacting repressor, that determines the mechanism of repression. Silencers form an intrinsic part of many eukaryotic promoters and, consequently, knowledge of their interactive role with enchancers and other transcriptional elements is essential for our understanding of gene regulation in eukaryotes.

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Hwang, Soonkyu, Namil Lee, Yujin Jeong, Yongjae Lee, Woori Kim, Suhyung Cho, Bernhard O. Palsson, and Byung-Kwan Cho. "Primary transcriptome and translatome analysis determines transcriptional and translational regulatory elements encoded in the Streptomyces clavuligerus genome." Nucleic Acids Research 47, no. 12 (May 27, 2019): 6114–29. http://dx.doi.org/10.1093/nar/gkz471.

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AbstractDetermining transcriptional and translational regulatory elements in GC-rich Streptomyces genomes is essential to elucidating the complex regulatory networks that govern secondary metabolite biosynthetic gene cluster (BGC) expression. However, information about such regulatory elements has been limited for Streptomyces genomes. To address this limitation, a high-quality genome sequence of β-lactam antibiotic-producing Streptomyces clavuligerus ATCC 27 064 is completed, which contains 7163 newly annotated genes. This provides a fundamental reference genome sequence to integrate multiple genome-scale data types, including dRNA-Seq, RNA-Seq and ribosome profiling. Data integration results in the precise determination of 2659 transcription start sites which reveal transcriptional and translational regulatory elements, including −10 and −35 promoter components specific to sigma (σ) factors, and 5′-untranslated region as a determinant for translation efficiency regulation. Particularly, sequence analysis of a wide diversity of the −35 components enables us to predict potential σ-factor regulons, along with various spacer lengths between the −10 and −35 elements. At last, the primary transcriptome landscape of the β-lactam biosynthetic pathway is analyzed, suggesting temporal changes in metabolism for the synthesis of secondary metabolites driven by transcriptional regulation. This comprehensive genetic information provides a versatile genetic resource for rational engineering of secondary metabolite BGCs in Streptomyces.

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Li, Junhua, Jinhong Yuan, and Mingjun Li. "Characterization of Putativecis-Regulatory Elements in Genes Preferentially Expressed inArabidopsisMale Meiocytes." BioMed Research International 2014 (2014): 1–10. http://dx.doi.org/10.1155/2014/708364.

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Meiosis is essential for plant reproduction because it is the process during which homologous chromosome pairing, synapsis, and meiotic recombination occur. The meiotic transcriptome is difficult to investigate because of the size of meiocytes and the confines of anther lobes. The recent development of isolation techniques has enabled the characterization of transcriptional profiles in male meiocytes ofArabidopsis. Gene expression in male meiocytes shows unique features. The direct interaction of transcription factors (TFs) with DNA regulatory sequences forms the basis for the specificity of transcriptional regulation. Here, we identified putativecis-regulatory elements (CREs) associated with male meiocyte-expressed genes usingin silicotools. The upstream regions (1 kb) of the top 50 genes preferentially expressed inArabidopsismeiocytes possessed conserved motifs. These motifs are putative binding sites of TFs, some of which share common functions, such as roles in cell division. In combination with cell-type-specific analysis, our findings could be a substantial aid for the identification and experimental verification of the protein-DNA interactions for the specific TFs that drive gene expression in meiocytes.

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van Hijum, Sacha A. F. T., Marnix H. Medema, and Oscar P. Kuipers. "Mechanisms and Evolution of Control Logic in Prokaryotic Transcriptional Regulation." Microbiology and Molecular Biology Reviews 73, no. 3 (September 2009): 481–509. http://dx.doi.org/10.1128/mmbr.00037-08.

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SUMMARY A major part of organismal complexity and versatility of prokaryotes resides in their ability to fine-tune gene expression to adequately respond to internal and external stimuli. Evolution has been very innovative in creating intricate mechanisms by which different regulatory signals operate and interact at promoters to drive gene expression. The regulation of target gene expression by transcription factors (TFs) is governed by control logic brought about by the interaction of regulators with TF binding sites (TFBSs) in cis-regulatory regions. A factor that in large part determines the strength of the response of a target to a given TF is motif stringency, the extent to which the TFBS fits the optimal TFBS sequence for a given TF. Advances in high-throughput technologies and computational genomics allow reconstruction of transcriptional regulatory networks in silico. To optimize the prediction of transcriptional regulatory networks, i.e., to separate direct regulation from indirect regulation, a thorough understanding of the control logic underlying the regulation of gene expression is required. This review summarizes the state of the art of the elements that determine the functionality of TFBSs by focusing on the molecular biological mechanisms and evolutionary origins of cis-regulatory regions.

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Olsen, Anders Krüger, Mette Boyd, Erik Thomas Danielsen, and Jesper Thorvald Troelsen. "Current and emerging approaches to define intestinal epithelium-specific transcriptional networks." American Journal of Physiology-Gastrointestinal and Liver Physiology 302, no. 3 (February 2012): G277—G286. http://dx.doi.org/10.1152/ajpgi.00362.2011.

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Upon developmental or environmental cues, the composition of transcription factors in a transcriptional regulatory network is deeply implicated in controlling the signature of the gene expression and thereby specifies the cell or tissue type. Novel methods including ChIP-chip and ChIP-Seq have been applied to analyze known transcription factors and their interacting regulatory DNA elements in the intestine. The intestine is an example of a dynamic tissue where stem cells in the crypt proliferate and undergo a differentiation process toward the villus. During this differentiation process, specific regulatory networks of transcription factors are activated to target specific genes, which determine the intestinal cell fate. The expanding genomewide mapping of transcription factor binding sites and construction of transcriptional regulatory networks provide new insight into how intestinal differentiation occurs. This review summarizes the current overview of the transcriptional regulatory networks driving epithelial differentiation in adult intestine. The novel technologies that have been implied to study these networks are presented and their prospects for implications in future research are also addressed.

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Dowen, Jill M., Steve Bilodeau, David A. Orlando, Michael R. Hübner, Brian J. Abraham, David L. Spector, and Richard A. Young. "Multiple Structural Maintenance of Chromosome Complexes at Transcriptional Regulatory Elements." Stem Cell Reports 1, no. 5 (November 2013): 371–78. http://dx.doi.org/10.1016/j.stemcr.2013.09.002.

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Gray, Lisa C., Lei Pan, Abigail M. Dalzell, Rossen M. Donev, Timothy R. Hughes, and Carmen W. van den Berg. "Transcriptional regulatory elements of the decay accelerating factor (DAF) gene." Molecular Immunology 44, no. 16 (September 2007): 3963. http://dx.doi.org/10.1016/j.molimm.2007.06.127.

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Venepally, P., D. Chen, and B. Kemper. "Transcriptional regulatory elements for basal expression of cytochrome P450IIC genes." Journal of Biological Chemistry 267, no. 24 (October 1992): 17333–38. http://dx.doi.org/10.1016/s0021-9258(18)41930-8.

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Ohgino, Y., F. Hattori, Y. Satoh, M. Yoichi, S. Tohyama, H. Yamashita, K. Yamabe, and K. Fukuda. "P496A novel atria specific gene and its transcriptional regulatory elements." Cardiovascular Research 103, suppl 1 (June 27, 2014): S90.5—S90. http://dx.doi.org/10.1093/cvr/cvu091.170.

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Lisziewicz, J., J. Brown, D. Breviario, T. Sreenath, N. Ahmed, R. Koller, and R. Dhar. "Transcriptional regulatory elements of the RAS2 gene of Saccharomyces cerevisiae." Nucleic Acids Research 18, no. 14 (1990): 4167–74. http://dx.doi.org/10.1093/nar/18.14.4167.

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Journal articles on the topic 'Transcriptional Regulatory Elements'

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