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Articles de revues sur le sujet « Hox clusters »

Auteur : Grafiati
Publié le 4 juin 2021
Mis à jour le 1 février 2022

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1

Darbellay, Fabrice, Célia Bochaton, Lucille Lopez-Delisle, Bénédicte Mascrez, Patrick Tschopp, Saskia Delpretti, Jozsef Zakany et Denis Duboule. « The constrained architecture of mammalian Hox gene clusters ». Proceedings of the National Academy of Sciences 116, no 27 (17 juin 2019) : 13424–33. http://dx.doi.org/10.1073/pnas.1904602116.

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In many animal species with a bilateral symmetry, Hox genes are clustered either at one or at several genomic loci. This organization has a functional relevance, as the transcriptional control applied to each gene depends upon its relative position within the gene cluster. It was previously noted that vertebrate Hox clusters display a much higher level of genomic organization than their invertebrate counterparts. The former are always more compact than the latter, they are generally devoid of repeats and of interspersed genes, and all genes are transcribed by the same DNA strand, suggesting that particular factors constrained these clusters toward a tighter structure during the evolution of the vertebrate lineage. Here, we investigate the importance of uniform transcriptional orientation by engineering several alleles within the HoxD cluster, such as to invert one or several transcription units, with or without a neighboring CTCF site. We observe that the association between the tight structure of mammalian Hox clusters and their regulation makes inversions likely detrimental to the proper implementation of this complex genetic system. We propose that the consolidation of Hox clusters in vertebrates, including transcriptional polarity, evolved in conjunction with the emergence of global gene regulation via the flanking regulatory landscapes, to optimize a coordinated response of selected subsets of target genes in cis.
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De Kumar, Bony, et Robb Krumlauf. « HOXs and lincRNAs : Two sides of the same coin ». Science Advances 2, no 1 (janvier 2016) : e1501402. http://dx.doi.org/10.1126/sciadv.1501402.

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The clustered Hox genes play fundamental roles in regulation of axial patterning and elaboration of the basic body plan in animal development. There are common features in the organization and regulatory landscape of Hox clusters associated with their highly conserved functional roles. The presence of transcribed noncoding sequences embedded within the vertebrate Hox clusters is providing insight into a new layer of regulatory information associated with Hox genes.
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Ruddle, Frank H., Kevin L. Bentley, Michael T. Murtha et Neil Risch. « Gene loss and gain in the evolution of the vertebrates ». Development 1994, Supplement (1 janvier 1994) : 155–61. http://dx.doi.org/10.1242/dev.1994.supplement.155.

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Homeobox cluster genes (Hox genes) are highly conserved and can be usefully employed to study phyletic relationships and the process of evolution itself. A phylogenetic survey of Hox genes shows an increase in gene number in some more recently evolved forms, particularly in vertebrates. The gene increase has occurred through a two-step process involving first, gene expansion to form a cluster, and second, cluster duplication to form multiple clusters. We also describe data that suggests that non-Hox genes may be preferrentially associated with the Hox clusters and raise the possibility that this association may have an adaptive biological function. Hox gene loss may also play a role in evolution. Hox gene loss is well substantiated in the vertebrates, and we identify additional possible instances of gene loss in the echinoderms and urochordates based on PCR surveys. We point out the possible adaptive role of gene loss in evolution, and urge the extension of gene mapping studies to relevant species as a means of its substantiation.
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Novikova, Elena L., et Milana A. Kulakova. « There and Back Again : Hox Clusters Use Both DNA Strands ». Journal of Developmental Biology 9, no 3 (15 juillet 2021) : 28. http://dx.doi.org/10.3390/jdb9030028.

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Bilaterian animals operate the clusters of Hox genes through a rich repertoire of diverse mechanisms. In this review, we will summarize and analyze the accumulated data concerning long non-coding RNAs (lncRNAs) that are transcribed from sense (coding) DNA strands of Hox clusters. It was shown that antisense regulatory RNAs control the work of Hox genes in cis and trans, participate in the establishment and maintenance of the epigenetic code of Hox loci, and can even serve as a source of regulatory peptides that switch cellular energetic metabolism. Moreover, these molecules can be considered as a force that consolidates the cluster into a single whole. We will discuss the examples of antisense transcription of Hox genes in well-studied systems (cell cultures, morphogenesis of vertebrates) and bear upon some interesting examples of antisense Hox RNAs in non-model Protostomia.
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Balavoine, Guillaume, Renaud de Rosa et André Adoutte. « Hox clusters and bilaterian phylogeny ». Molecular Phylogenetics and Evolution 24, no 3 (septembre 2002) : 366–73. http://dx.doi.org/10.1016/s1055-7903(02)00237-3.

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Krumlauf, Robb. « Hox genes, clusters and collinearity ». International Journal of Developmental Biology 62, no 11-12 (2018) : 659–63. http://dx.doi.org/10.1387/ijdb.180330rr.

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This year marks the 40th anniversary of the discovery by Ed Lewis of the property of collinearity in the bithorax gene complex in Drosophila. This landmark work illustrated the need to understand regulatory mechanisms that coordinate expression of homeotic gene clusters. Through the efforts of many groups, investigation of the Hox gene family has generated many fundamental findings on the roles and regulation of this conserved gene family in development, disease and evolution. This has led to a number of important conceptual advances in gene regulation and evolutionary biology. This article presents some of the history and advances made through studies on Hox gene clusters.
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Prince, V. E., L. Joly, M. Ekker et R. K. Ho. « Zebrafish hox genes : genomic organization and modified colinear expression patterns in the trunk ». Development 125, no 3 (1 février 1998) : 407–20. http://dx.doi.org/10.1242/dev.125.3.407.

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The Hox genes are implicated in conferring regional identity to the anteroposterior axis of the developing embryo. We have characterized the organization and expression of hox genes in the teleost zebrafish (Danio rerio), and compared our findings with those made for the tetrapod vertebrates. We have isolated 32 zebrafish hox genes, primarily via 3′RACE-PCR, and analyzed their linkage relationships using somatic cell hybrids. We find that in comparison to the tetrapods, zebrafish has several additional hox genes, both within and beyond the expected 4 hox clusters (A-D). For example, we have isolated a member of hox paralogue group 8 lying on the hoxa cluster, and a member of hox paralogue group 10 lying on the b cluster, no equivalent genes have been reported for mouse or human. Beyond the 4 clusters (A-D) we have isolated a further 3 hox genes (the hoxx and y genes), which according to their sequence homologies lie in paralogue groups 4, 6, and 9. The hoxx4 and hoxx9 genes occur on the same set of hybrid chromosomes, hinting at the possibility of an additional hox cluster for the zebrafish. Similar to their tetrapod counterparts, zebrafish hox genes (including those with no direct tetrapod equivalent) demonstrate colinear expression along the anteroposterior (AP) axis of the embryo. However, in comparison to the tetrapods, anterior hox expression limits are compacted over a short AP region; some members of adjacent paralogue groups have equivalent limits. It has been proposed that during vertebrate evolution, the anterior limits of Hox gene expression have become dispersed along the AP axis allowing the genes to take on novel patterning roles and thus leading to increased axial complexity. In the teleost zebrafish, axial organization is relatively simple in comparison to that of the tetrapod vertebrates; this may be reflected by the less dispersed expression domains of the zebrafish hox genes.
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Drabkin, Harry, Sharvari Gadgil, Chan Zeng, Anna Baron et Olivier Bernard. « Homeodomain Expression in AML and T-ALL Cell Lines. » Blood 104, no 11 (16 novembre 2004) : 3369. http://dx.doi.org/10.1182/blood.v104.11.3369.3369.

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Abstract HOX genes are frequent targets of chromosomal translocations and retroviral integrations in human and murine acute leukemia, often involving genes at the 5′-end of the HOX clusters. We previously reported that HOX expression patterns in AML were related to prognostic cytogenetic subsets. We also identified a distinct subset of patients with intermediate cytogenetics based on high levels of HOX and FLT3 expression, frequent FLT3 mutations and a low incidence of C/EBPa mutations. Certain cases of T-ALL also have rearrangements of homeodomain genes and some T-ALLs express limited myeloid markers. To further explore the spectrum of homeodomain gene expression, we developed qRT-PCR assays for nearly all clustered HOXA-D genes, selected homeodomain genes on chromosomes often altered in AML, and selected polycomb (Pc) genes, FLT3 and MLL. Altogether, 52 genes were analyzed in 32 AML and T-ALL cell lines. FLT3 expression was confined to a subset of AMLs. HOX11, HOX11L2 and NKX2.5 were expressed only in cases involving rearrangements of these genes. The Pc and MLL genes were uniformly expressed. Among HOX clusters, the frequency of gene expression was HOXA>B>C>D. Genes more highly expressed in the HOXC and D clusters were those at the 5′-ends (e.g., D13, C10). Marked or selective overexpression of individual genes suggests their possible involvement in the disease process, immortalization or differentiation. Examples include EN1 (SUPT1), D13 (MEGA1, B9 (PEER). A hierarchical cluster analysis based on homeodomain genes successfully identified subsets of related cell lines. Thus, the analysis of quantitative HOX expression may provide an important new tool to better understand the biology of acute leukemia.
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Papageorgiou, Spyros. « Hox Gene Collinearity May Be Related to Noether Theory on Symmetry and Its Linked Conserved Quantity ». J — Multidisciplinary Scientific Journal 3, no 2 (24 avril 2020) : 151–61. http://dx.doi.org/10.3390/j3020013.

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Hox Gene Collinearity (HGC) is a fundamental property that controls the development of many animal species, including vertebrates. In the Hox gene clusters, the genes are located in a sequential order Hox1, Hox2, Hox3, etc., along the 3’ to 5’ direction of the cluster in the chromosome. During Hox cluster activation, the Hox genes are expressed sequentially in the ontogenetic units D1, D2, D3, etc., along the anterior–posterior axis (A-P) of the early embryo. This collinearity, first observed by E.B. Lewis, is surprising because the spatial collinearity of these structures (Hox clusters and embryos) correlates entities that differ by about four orders of magnitude. Biomolecular mechanisms alone cannot explain such correlations. Long-range physical interactions, such as diffusion or electric attractions, should be involved. A biophysical model (BM) was formulated, which, in alignment with the biomolecular processes, successfully describes the existing vertebrate genetic engineering data. One hundred years ago, Emmy Noether made a fundamental discovery in mathematics and physics. She proved, rigorously, that a physical system obeying a symmetry law (e.g., rotations or self-similarity) is followed by a conserved physical quantity. It is argued here that HGC obeys a ‘primitive’ self-similarity symmetry. In this case, the associated primitive conserved quantity is the irreversibly increasing ‘ratchet’-like Hoxgene ordering where some genes may be missing. The genes of a vertebrate Hox clusterare located along a finite straight line. The same order follows the ontogenetic unitsof the vertebrate embryo. Therefore, HGC is a manifestation of a primitive Noether Theory (NT). NT may be applied to other than the vertebrate case, for instance, to animals with a circular topological symmetry. For example, the observed abnormal Hox gene ordering of the echinoderm Hox clusters may be reproduced by a double-strand break of the circular Hox gene ordering and its subsequent incorporation in the flanking chromosome.
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Schiemann, Sabrina M., José M. Martín-Durán, Aina Børve, Bruno C. Vellutini, Yale J. Passamaneck et Andreas Hejnol. « Clustered brachiopod Hox genes are not expressed collinearly and are associated with lophotrochozoan novelties ». Proceedings of the National Academy of Sciences 114, no 10 (22 février 2017) : E1913—E1922. http://dx.doi.org/10.1073/pnas.1614501114.

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Temporal collinearity is often considered the main force preserving Hox gene clusters in animal genomes. Studies that combine genomic and gene expression data are scarce, however, particularly in invertebrates like the Lophotrochozoa. As a result, the temporal collinearity hypothesis is currently built on poorly supported foundations. Here we characterize the complement, cluster, and expression of Hox genes in two brachiopod species,Terebratalia transversaandNovocrania anomala.T. transversahas a split cluster with 10 genes (lab,pb,Hox3,Dfd,Scr,Lox5,Antp,Lox4,Post2, andPost1), whereasN. anomalahas 9 genes (apparently missingPost1). Our in situ hybridization, real-time quantitative PCR, and stage-specific transcriptomic analyses show that brachiopod Hox genes are neither strictly temporally nor spatially collinear; onlypb(inT. transversa),Hox3(in both brachiopods), andDfd(in both brachiopods) show staggered mesodermal expression. Thus, our findings support the idea that temporal collinearity might contribute to keeping Hox genes clustered. Remarkably, expression of the Hox genes in both brachiopod species demonstrates cooption of Hox genes in the chaetae and shell fields, two major lophotrochozoan morphological novelties. The shared and specific expression of Hox genes, together withArx,Zic, and Notch pathway components in chaetae and shell fields in brachiopods, mollusks, and annelids provide molecular evidence supporting the conservation of the molecular basis for these lophotrochozoan hallmarks.
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Zeltser, L., C. Desplan et N. Heintz. « Hoxb-13 : a new Hox gene in a distant region of the HOXB cluster maintains colinearity ». Development 122, no 8 (1 août 1996) : 2475–84. http://dx.doi.org/10.1242/dev.122.8.2475.

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The Hox genes are involved in patterning along the A/P axes of animals. The clustered organization of Hox genes is conserved from nematodes to vertebrates. During evolution, the number of Hox genes within the ancestral complex increased, exemplified by the five-fold amplification of the AbdB-related genes, leading to a total number of thirteen paralogs. This was followed by successive duplications of the cluster to give rise to the four vertebrate HOX clusters. A specific subset of paralogs was subsequently lost from each cluster, yet the composition of each cluster was likely conserved during tetrapod evolution. While the HOXA, HOXC and HOXD clusters contain four to five AbdB-related genes, only one gene (Hoxb-9) is found in the HOXB complex. We have identified a new member of paralog group 13 in human and mouse, and shown that it is in fact Hoxb-13. A combination of genetic and physical mapping demonstrates that the new gene is found approx. 70 kb upstream of Hoxb-9 in the same transcriptional orientation as the rest of the cluster. Despite its relatively large distance from the HOX complex, Hoxb-13 exhibits temporal and spatial colinearity in the main body axis of the mouse embryo. The onset of transcription occurs at E9.0 in the tailbud region. At later stages of development, Hoxb-13 is expressed in the tailbud and posterior domains in the spinal cord, digestive tract and urogenital system. However, it is not expressed in the secondary axes such as the limbs and genital tubercle. These results indicate that the 5′ end of the HOXB cluster has not been lost and that at least one member exists and is highly conserved among different vertebrate species. Because of its separation from the complex, Hoxb-13 may provide an important system to dissect the mechanism(s) responsible for the maintenance of colinearity.
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Lemons, D. « Genomic Evolution of Hox Gene Clusters ». Science 313, no 5795 (29 septembre 2006) : 1918–22. http://dx.doi.org/10.1126/science.1132040.

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Gaunt, Stephen J. « Hox cluster genes and collinearities throughout the tree of animal life ». International Journal of Developmental Biology 62, no 11-12 (2018) : 673–83. http://dx.doi.org/10.1387/ijdb.180162sg.

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The discovery of Hox gene clusters, first in Drosophila (a protostome) and then as homologues in vertebrates (deuterostomes), was a major step in our understanding of both developmental and evolutionary biology. Hox genes in both species perform the same overall function: that is, organization of the body along its head-tail axis. The conclusion is that the protostome-deuterostome ancestor, founder of 99% of all described animal species, must already have had this same basic Hox cluster, and that it probably used it in the same way to establish its body plan. A striking feature of Hox genes is the spatial collinearity rule: that order of the genes along the chromosome corresponds with the order of their expression domains along the embryo. For vertebrates, though not Drosophila, there is also the temporal collinearity rule: that order of genes along the chromosome corresponds with timing of Hox expressions in the embryo. Although Hox genes are clearly recognized in pre-bilaterians (Cnidaria), it is only in bilaterians that the characteristic clustered Hox arrangement and function is commonly found. Spatial collinearity in expression is conserved widely throughout Bilateria but temporal collinearity is so far limited to vertebrates, cephalochordates, and some arthropods and annelids. In addition to conserved use of Hox genes to pattern the head-tail axis, some animal groups, particularly lophotrochozoans, have extensively co-opted Hox genes, outside collinearity rules, to regulate development of novel structures. Satisfactory understanding of Hox cluster function requires better understanding of the bilaterian last common ancestor (Urbilateria). Xenacoelomorpha may provide useful living models of the ancestral bilaterian condition.
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Amores, A. « Zebrafish hox Clusters and Vertebrate Genome Evolution ». Science 282, no 5394 (27 novembre 1998) : 1711–14. http://dx.doi.org/10.1126/science.282.5394.1711.

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Apiou, F., D. Flagiello, C. Cillo, B. Malfoy, M. F. Poupon et B. Dutrillaux. « Fine mapping of human HOX gene clusters ». Cytogenetic and Genome Research 73, no 1-2 (1996) : 114–15. http://dx.doi.org/10.1159/000134320.

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Kharchenko, P. V., C. J. Woo, M. Y. Tolstorukov, R. E. Kingston et P. J. Park. « Nucleosome positioning in human HOX gene clusters ». Genome Research 18, no 10 (7 août 2008) : 1554–61. http://dx.doi.org/10.1101/gr.075952.107.

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Pascual-Anaya, Juan, Salvatore D’Aniello, Shigeru Kuratani et Jordi Garcia-Fernàndez. « Evolution of Hox gene clusters in deuterostomes ». BMC Developmental Biology 13, no 1 (2013) : 26. http://dx.doi.org/10.1186/1471-213x-13-26.

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Noordermeer, D., M. Leleu, E. Splinter, J. Rougemont, W. De Laat et D. Duboule. « The Dynamic Architecture of Hox Gene Clusters ». Science 334, no 6053 (13 octobre 2011) : 222–25. http://dx.doi.org/10.1126/science.1207194.

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Galliot, B., P. Dolle, M. Vigneron, M. S. Featherstone, A. Baron et D. Duboule. « The mouse Hox-1.4 gene : primary structure, evidence for promoter activity and expression during development ». Development 107, no 2 (1 octobre 1989) : 343–59. http://dx.doi.org/10.1242/dev.107.2.343.

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This study reports the structure of the mouse homeobox-containing gene Hox-1.4 of the HOX-1 cluster, as well as its expression pattern during embryonic and fetal development. The overall structure of this gene includes two major exons, the second of which encodes the homeo-domain. The putative Hox-1.4 protein displays similarities with products of homologous genes located at the same relative positions in other HOX clusters. A fragment extending 360 base pairs (bp) upstream of a transcriptional start site was shown to be able to promote transcription in transfected cells. This fragment is GC-rich and contains binding sites for the Sp1 transcription factor. In situ hybridization studies revealed the Hox-1.4 expression pattern during development. As already reported for several other murine Hox genes, Hox-1.4 is expressed in the fetal central nervous system (CNS), in structures derived from somitic mesodermal condensations (sclerotomes, prevertebrae) as well as in several mesodermal components of various organs and structures such as lungs, gut, stomach, intestine and meso- and metanephros. This expression pattern is in good agreement with recent proposals concerning the involvement of such genes in the establishment of the vertebrate body plan as well as the relationship between the positions of these genes within their clusters and the anteroposterior restriction of their expression domains.
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Simon, H. G., et C. J. Tabin. « Analysis of Hox-4.5 and Hox-3.6 expression during newt limb regeneration : differential regulation of paralogous Hox genes suggest different roles for members of different Hox clusters ». Development 117, no 4 (1 avril 1993) : 1397–407. http://dx.doi.org/10.1242/dev.117.4.1397.

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Adult urodele amphibians can regenerate their limbs and tail. Based on their roles in other developing systems, Hox genes are strong candidates for genes that play a role in regulating pattern formation during regeneration. There are four homologous clusters of Hox genes in vertebrate genomes. We isolated cDNA clones of two newt homeobox genes from homologous positions within two Hox clusters; Hox-4.5 and Hox-3.6. We used RNase protection on nonamputated (normal) and regenerating newt appendages and tissue to compare their transcriptional patterns. Both genes show increased expression upon amputation with similar kinetics. Hox-4.5 and Hox-3.6 transcription is limited to the mesenchymal cells in the regenerates and is not found in the epithelial tissue. In addition to regenerating appendages, both genes are transcriptionally active in adult kidney of the newt. Striking differences were found in the regulation of Hox-4.5 and Hox-3.6 when they were compared in unamputated limbs and in regenerating forelimbs versus regenerating hindlimbs. Hox-4.5 is expressed in the blastema of regenerating fore- and hindlimbs, but Hox-4.5 transcripts are not detectable in normal limbs. In contrast, Hox-3.6 transcripts are found exclusively in posterior appendages, but are present in normal as well as regenerating hindlimbs and tails. Hox-4.5 is also expressed at a higher level in proximal (mid-humerus) regenerates than in distal ones (mid-radius). When we proximalized the positional memory of a distal blastema with retinoic acid, we find that the early expression level of Hox-4.5 is also proximalized. When the expression of these genes is compared to the expression of two previously reported newt Hox genes, a consistent pattern emerges, which can be interpreted in terms of differential roles for the different Hox clusters in determining regenerative limb morphology.
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Botti, Gerardo, Clemente Cillo, Rossella De Cecio, Maria Gabriella Malzone et Monica Cantile. « Paralogous HOX13 Genes in Human Cancers ». Cancers 11, no 5 (20 mai 2019) : 699. http://dx.doi.org/10.3390/cancers11050699.

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Hox genes (HOX in humans), an evolutionary preserved gene family, are key determinants of embryonic development and cell memory gene program. Hox genes are organized in four clusters on four chromosomal loci aligned in 13 paralogous groups based on sequence homology (Hox gene network). During development Hox genes are transcribed, according to the rule of “spatio-temporal collinearity”, with early regulators of anterior body regions located at the 3’ end of each Hox cluster and the later regulators of posterior body regions placed at the distal 5’ end. The onset of 3’ Hox gene activation is determined by Wingless-type MMTV integration site family (Wnt) signaling, whereas 5’ Hox activation is due to paralogous group 13 genes, which act as posterior-inhibitors of more anterior Hox proteins (posterior prevalence). Deregulation of HOX genes is associated with developmental abnormalities and different human diseases. Paralogous HOX13 genes (HOX A13, HOX B13, HOX C13 and HOX D13) also play a relevant role in tumor development and progression. In this review, we will discuss the role of paralogous HOX13 genes regarding their regulatory mechanisms during carcinogenesis and tumor progression and their use as biomarkers for cancer diagnosis and treatment.
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Paço, Ana, Simone Aparecida de Bessa Garcia et Renata Freitas. « Methylation in HOX Clusters and Its Applications in Cancer Therapy ». Cells 9, no 7 (3 juillet 2020) : 1613. http://dx.doi.org/10.3390/cells9071613.

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HOX genes are commonly known for their role in embryonic development, defining the positional identity of most structures along the anterior–posterior axis. In postembryonic life, HOX gene aberrant expression can affect several processes involved in tumorigenesis such as proliferation, apoptosis, migration and invasion. Epigenetic modifications are implicated in gene expression deregulation, and it is accepted that methylation events affecting HOX gene expression play crucial roles in tumorigenesis. In fact, specific methylation profiles in the HOX gene sequence or in HOX-associated histones are recognized as potential biomarkers in several cancers, helping in the prediction of disease outcomes and adding information for decisions regarding the patient’s treatment. The methylation of some HOX genes can be associated with chemotherapy resistance, and its identification may suggest the use of other treatment options. The use of epigenetic drugs affecting generalized or specific DNA methylation profiles, an approach that now deserves much attention, seems likely to be a promising weapon in cancer therapy in the near future. In this review, we summarize these topics, focusing particularly on how the regulation of epigenetic processes may be used in cancer therapy.
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Montavon, Thomas, et Denis Duboule. « Chromatin organization and global regulation of Hox gene clusters ». Philosophical Transactions of the Royal Society B : Biological Sciences 368, no 1620 (19 juin 2013) : 20120367. http://dx.doi.org/10.1098/rstb.2012.0367.

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During development, a properly coordinated expression of Hox genes, within their different genomic clusters is critical for patterning the body plans of many animals with a bilateral symmetry. The fascinating correspondence between the topological organization of Hox clusters and their transcriptional activation in space and time has served as a paradigm for understanding the relationships between genome structure and function. Here, we review some recent observations, which revealed highly dynamic changes in the structure of chromatin at Hox clusters, in parallel with their activation during embryonic development. We discuss the relevance of these findings for our understanding of large-scale gene regulation.
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Mathews, CH, K. Detmer, E. Boncinelli, HJ Lawrence et C. Largman. « Erythroid-restricted expression of homeobox genes of the human HOX 2 locus ». Blood 78, no 9 (1 novembre 1991) : 2248–52. http://dx.doi.org/10.1182/blood.v78.9.2248.2248.

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Abstract We have previously reported that certain members of the HOX 1 and HOX 2 clusters of class 1 homeobox-containing genes showed lineage-restricted patterns of expression in a small series of human hematopoietic cell lines. We now report on the expression patterns of the entire HOX 2 cluster, consisting of nine homeobox genes, in a broad survey of leukemic cell lines of different phenotypes. The most striking observation is that all but one of the HOX 2 genes are consistently expressed in cells with erythroid character and/or potential, but, with rare exception, not in cells with myelomonocytic or T- or B-lymphoid phenotype. By contrast, several genes of the HOX 1 and 3 loci are not expressed in erythroid lines. Within erythroid cell lines, many of the HOX 2 genes are expressed as multiple transcripts. Expression of some HOX 2 genes is detectable in normal human marrow. These data show that in human hematopoietic cell lines HOX 2 homeobox gene expression is largely restricted to cells of erythroid phenotype and suggest that these genes play a role in erythropoiesis.
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Mathews, CH, K. Detmer, E. Boncinelli, HJ Lawrence et C. Largman. « Erythroid-restricted expression of homeobox genes of the human HOX 2 locus ». Blood 78, no 9 (1 novembre 1991) : 2248–52. http://dx.doi.org/10.1182/blood.v78.9.2248.bloodjournal7892248.

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We have previously reported that certain members of the HOX 1 and HOX 2 clusters of class 1 homeobox-containing genes showed lineage-restricted patterns of expression in a small series of human hematopoietic cell lines. We now report on the expression patterns of the entire HOX 2 cluster, consisting of nine homeobox genes, in a broad survey of leukemic cell lines of different phenotypes. The most striking observation is that all but one of the HOX 2 genes are consistently expressed in cells with erythroid character and/or potential, but, with rare exception, not in cells with myelomonocytic or T- or B-lymphoid phenotype. By contrast, several genes of the HOX 1 and 3 loci are not expressed in erythroid lines. Within erythroid cell lines, many of the HOX 2 genes are expressed as multiple transcripts. Expression of some HOX 2 genes is detectable in normal human marrow. These data show that in human hematopoietic cell lines HOX 2 homeobox gene expression is largely restricted to cells of erythroid phenotype and suggest that these genes play a role in erythropoiesis.
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Prohaska, Sonja J., Claudia Fried, Christoph Flamm, Günter P. Wagner et Peter F. Stadler. « Surveying phylogenetic footprints in large gene clusters : applications to Hox cluster duplications ». Molecular Phylogenetics and Evolution 31, no 2 (mai 2004) : 581–604. http://dx.doi.org/10.1016/j.ympev.2003.08.009.

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Shahhoseini, Maryam, Zeinab Taghizadeh, Maryam Hatami et Hossein Baharvand. « Retinoic acid dependent histone 3 demethylation of the clustered HOX genes during neural differentiation of human embryonic stem cells ». Biochemistry and Cell Biology 91, no 2 (avril 2013) : 116–22. http://dx.doi.org/10.1139/bcb-2012-0049.

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Gene activation of HOX clusters is an early event in embryonic development. These genes are highly expressed and active in the vertebrate nervous system. Based on the presence of retinoic acid response elements (RAREs) in the regulatory region of many of the HOX genes, it is deduced that retinoic acid (RA) can influence epigenetic regulation and consequently the expression pattern of HOX during RA-induced differentiation of embryonic model systems. In this investigation, the expression level as well as the epigenetic regulation of several HOX genes of the 4 A–D clusters was analyzed in human embryonic stem cells, and also through their neural induction, in the presence and absence of RA. Expression analysis data significantly showed increased mRNA levels of all examined HOX genes in the presence of RA. Epigenetic analysis of the HOX gene regulatory regions also showed a significant decrease in methylation of histone H3K27 parallel to an absolute preferential incorporation of the demethylase UTX rather than JMJD3 in RA-induced neural differentiated cells. This finding clearly showed the functional role of UTX in epigenetic alteration of HOX clusters during RA-induced neural differentiation; the activity could not be detectable for the demethylase JMJD3 during this developmental process.
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Hoegg, Simone, et Axel Meyer. « Hox clusters as models for vertebrate genome evolution ». Trends in Genetics 21, no 8 (août 2005) : 421–24. http://dx.doi.org/10.1016/j.tig.2005.06.004.

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Duboule, D. « The rise and fall of Hox gene clusters ». Development 134, no 14 (6 juin 2007) : 2549–60. http://dx.doi.org/10.1242/dev.001065.

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Freeman, Robert, Tetsuro Ikuta, Michael Wu, Ryo Koyanagi, Takeshi Kawashima, Kunifumi Tagawa, Tom Humphreys et al. « Identical Genomic Organization of Two Hemichordate Hox Clusters ». Current Biology 22, no 21 (novembre 2012) : 2053–58. http://dx.doi.org/10.1016/j.cub.2012.08.052.

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Ogishima, Soichi, et Hiroshi Tanaka. « Missing link in the evolution of Hox clusters ». Gene 387, no 1-2 (janvier 2007) : 21–30. http://dx.doi.org/10.1016/j.gene.2006.08.011.

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Hunt, Paul, Jenny Whiting, Stefan Nonchev, Mai-Har Sham, Heather Marshall, Antony Graham, Martyn Cook et al. « The branchial Hox code and its implications for gene regulation, patterning of the nervous system and head evolution ». Development 113, Supplement_2 (1 avril 1991) : 63–77. http://dx.doi.org/10.1242/dev.113.supplement_2.63.

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In this study we have examined the expression of murine Hox homeobox containing genes by in situ hybridisation in the branchial region of the head. Genes from the Hox complexes display segmentally restricted domains of expression in the developing hindbrain, which are correlated with similar restricted domains in the neural crest and surface ectoderm of the branchial arches. Comparison of related genes from the different clusters shows that subfamily members are expressed in identical rhombomeres and branchial arches. These patterns suggest a combinatorial system for specifying regional variation in the head, which we refer to as a Hox code. The Hox genes also display dynamic dorso-ventral (D-V) restrictions in the developing neural tube which mirror the timing and spatial distributions of the birth of major classes of neurons in the CNS. Genes in the Hox-2 cluster all have a similar D-V distribution that differs from that of genes from the other Hox clusters, and suggests that members of a subfamily may be used to specify positional values to different subsets of cells at the same axial level. These results are discussed in terms of a system for patterning the branchial regions of the vertebrate head, and evolution of head structures. We have also examined aspects of the transcriptional regulation of Hox-2 genes in transgenic mice using a lacZ reporter gene. We have been able to reconstruct the major pattern of the Hox-2.6 gene on the basis of identical expression of the transgene and the endogenous gene with respect to timing, spatial restrictions and tissue-specific distributions. Deletion analysis has enabled us to identify three regions involved in generating this pattern. Two of these regions have the properties of enhancers which are capable of imposing spatiallyrestricted domains of expression on heterologous promoters. We have generated similar Hox-lacZ fusions that reconstruct the highly restricted patterns of the Hox-2.1 and Hox-2.8 genes in the developing nervous system, supporting our in situ analysis and the idea of a Hox code. These transgenic experiments are a useful step in examining regulation in the Hox cascade.
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Aparicio, Samuel, Kelvin Hawker, Amanda Cottage, Yoshikazu Mikawa, Lin Zuo, Byrappa Venkatesh, Elson Chen, Robb Krumlauf et Sydney Brenner. « Organization of the Fugu rubripes Hox clusters : evidence for continuing evolution of vertebrate Hox complexes ». Nature Genetics 16, no 1 (mai 1997) : 79–83. http://dx.doi.org/10.1038/ng0597-79.

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Graham, A., M. Maden et R. Krumlauf. « The murine Hox-2 genes display dynamic dorsoventral patterns of expression during central nervous system development ». Development 112, no 1 (1 mai 1991) : 255–64. http://dx.doi.org/10.1242/dev.112.1.255.

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This report demonstrates that the genes in the murine Hox-2 cluster display spatially and temporally dynamic patterns of expression in the transverse plane of the developing CNS. All of the Hox-2 genes exhibit changing patterns of expression that reflect events during the ontogeny of the CNS. The observed expression correlates with the timing and location of the birth of major classes of neurons in the spinal cord. Therefore, it is suggested that the Hox-2 genes act to confer rostrocaudal positional information on each successive class of newly born neurons. This analysis has also revealed a striking dorsal restriction in the patterns of Hox-2 expression in the spinal cord between 12.5 and 14.5 days of gestation, which does not appear to correlate with any morphological structure. The cellular retinol binding protein (CRBP) shows a complementary ventral staining pattern, suggesting that a number of genes are dorsoventrally restricted during the development of the CNS. The expression of Hox-2 genes has also been compared with the Hox-3.1 gene, which exhibits a markedly different dorsoventral pattern of expression. This suggests that, while genes in the different murine Hox clusters may have similar A-P domains of expression, they are responding to different dorsoventral patterning signals in the developing spinal cord.
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Koh, E. G. L., K. Lam, A. Christoffels, M. V. Erdmann, S. Brenner et B. Venkatesh. « Hox gene clusters in the Indonesian coelacanth, Latimeria menadoensis ». Proceedings of the National Academy of Sciences 100, no 3 (23 janvier 2003) : 1084–88. http://dx.doi.org/10.1073/pnas.0237317100.

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Henkel, Christiaan V., Erik Burgerhout, Daniëlle L. de Wijze, Ron P. Dirks, Yuki Minegishi, Hans J. Jansen, Herman P. Spaink et al. « Primitive Duplicate Hox Clusters in the European Eel's Genome ». PLoS ONE 7, no 2 (24 février 2012) : e32231. http://dx.doi.org/10.1371/journal.pone.0032231.

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Mungpakdee, S., H. C. Seo, A. R. Angotzi, X. Dong, A. Akalin et D. Chourrout. « Differential Evolution of the 13 Atlantic Salmon Hox Clusters ». Molecular Biology and Evolution 25, no 7 (3 avril 2008) : 1333–43. http://dx.doi.org/10.1093/molbev/msn097.

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Kumar, Ashish R., et John H. Kersey. « The Expression of Genes 5′ in the Hox-A Cluster Is Co-Ordinated Both in Normal and Leukemic Hematopoiesis. » Blood 104, no 11 (16 novembre 2004) : 3560. http://dx.doi.org/10.1182/blood.v104.11.3560.3560.

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Hox genes are known to play critical roles in hematopoiesis and are probably important in the pathogenesis of leukemias. Disruption of the Hoxa9 gene in mice leads to defects in erythroid, lymphoid and myeloid hematopoiesis while over-expression of Hoxa9 leads to leukemia in mice. Transcription of Hoxa9 is partly regulated by the Mixed lineage leukemia gene (Mll) product. Bone marrow cells of mice carrying the leukemic Mll-AF9 fusion gene as a knock-in mutation (henceforth called Mll), display an increase in expression of several Hox genes - Hoxa5, Hoxa6, Hoxa7, Hoxa9 and Hoxa10, when compared to age matched wild type mice (Kumar et. al, 2004, Blood). Since the over-expressed Hox genes all belong to the same Hox-a cluster, we hypothesized that these genes might be co-regulated during normal hematopoiesis. Co-regulation of neighboring genes within the same cluster has been reported by others for the Hox-b and c clusters. To test this hypothesis for the 5′ Hox-a cluster genes, we compared expression levels of Hoxa5, Hox7 and Hoxa10 in Hoxa9 homozygous knockout (Hoxa9−/−) and wild type bone marrow by real-time quantitative RT-PCR using Taqman primers/probe sets (Applied Biosystems, CA). Expression levels of Hoxa5, Hoxa7, and Hoxa10 were all reduced by 65% ± 2% in Hoxa9−/− mice compared to wild type mice. In contrast, levels of Hoxb4 and Meis1 - homeobox genes that are not part of the Hox-a cluster - were identical in Hoxa9−/− and wild type mice. These results show no compensatory increases in expression of other 5′ Hox-a genes in the absence of Hoxa9, but instead demonstrate that disruption of Hoxa9 decreases the expression of neighboring genes in the Hox-a cluster. The hematopoietic defects seen in Hoxa9−/− mice (leucopenia, lymphopenia and blunted granulocytic response to G-CSF) might thus be attributable to the deficiency of multiple Hox-a gene products, rather than of Hoxa9 alone. To further evaluate the extent of this co-regulation, we studied the expression levels of these genes in Mll mice that lacked Hoxa9 (Hoxa9−/−/Mll-AF9+/−, henceforth called Mll/Hox). The Mll/Hox mice develop leukemia at the same rate and time course as the Mll mice, but with a phenotype that is relatively more immature. In Mll/Hox mice, the expression levels of Hoxa5 and Hoxa7 were increased 13 fold and 4 fold respectively, while those of Hoxa10 remained decreased at 35% of wild type. These results indicate that the decreased expression of neighboring Hox-a genes in Hoxa9−/− mice was reversed by Mll-AF9 for Hoxa5 and Hoxa7, but not for Hoxa10, suggesting a second level of co-regulation for Hoxa9 and Hoxa10. Overall, our findings demonstrate a co-regulated relationship between the 5′ Hox-a cluster genes during normal hematopoiesis, and provide evidence that deregulation of a single Hoxa9 gene significantly alters the expression of neighboring Hox-a cluster genes with implications for understanding the pathogenetic mechanisms of leukemia.
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Feiner, Nathalie, et Natalie J. Wood. « Lizards possess the most complete tetrapod Hox gene repertoire despite pervasive structural changes in Hox clusters ». Evolution & ; Development 21, no 4 (juillet 2019) : 218–28. http://dx.doi.org/10.1111/ede.12300.

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Langston, Alexander W., James R. Thompson et Lorraine J. Gudas. « Retinoic Acid-responsive Enhancers Located 3′ of the Hox A and Hox B Homeobox Gene Clusters ». Journal of Biological Chemistry 272, no 4 (24 janvier 1997) : 2167–75. http://dx.doi.org/10.1074/jbc.272.4.2167.

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Xu, Xiaocui, Guoqiang Li, Congru Li, Jing Zhang, Qiang Wang, David K. Simmons, Xuepeng Chen et al. « Evolutionary transition between invertebrates and vertebrates via methylation reprogramming in embryogenesis ». National Science Review 6, no 5 (24 mai 2019) : 993–1003. http://dx.doi.org/10.1093/nsr/nwz064.

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ABSTRACT Major evolutionary transitions are enigmas, and the most notable enigma is between invertebrates and vertebrates, with numerous spectacular innovations. To search for the molecular connections involved, we asked whether global epigenetic changes may offer a clue by surveying the inheritance and reprogramming of parental DNA methylation across metazoans. We focused on gametes and early embryos, where the methylomes are known to evolve divergently between fish and mammals. Here, we find that methylome reprogramming during embryogenesis occurs neither in pre-bilaterians such as cnidarians nor in protostomes such as insects, but clearly presents in deuterostomes such as echinoderms and invertebrate chordates, and then becomes more evident in vertebrates. Functional association analysis suggests that DNA methylation reprogramming is associated with development, reproduction and adaptive immunity for vertebrates, but not for invertebrates. Interestingly, the single HOX cluster of invertebrates maintains unmethylated status in all stages examined. In contrast, the multiple HOX clusters show dramatic dynamics of DNA methylation during vertebrate embryogenesis. Notably, the methylation dynamics of HOX clusters are associated with their spatiotemporal expression in mammals. Our study reveals that DNA methylation reprogramming has evolved dramatically during animal evolution, especially after the evolutionary transitions from invertebrates to vertebrates, and then to mammals.
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Sjöholm, Johannes, Paulo Oliveira et Peter Lindblad. « Transcription and Regulation of the Bidirectional Hydrogenase in the Cyanobacterium Nostoc sp. Strain PCC 7120 ». Applied and Environmental Microbiology 73, no 17 (13 juillet 2007) : 5435–46. http://dx.doi.org/10.1128/aem.00756-07.

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ABSTRACT The filamentous, heterocystous cyanobacterium Nostoc sp. strain PCC 7120 (Anabaena sp. strain PCC 7120) possesses an uptake hydrogenase and a bidirectional enzyme, the latter being capable of catalyzing both H2 production and evolution. The completely sequenced genome of Nostoc sp. strain PCC 7120 reveals that the five structural genes encoding the bidirectional hydrogenase (hoxEFUYH) are separated in two clusters at a distance of approximately 8.8 kb. The transcription of the hox genes was examined under nitrogen-fixing conditions, and the results demonstrate that the cluster containing hoxE and hoxF can be transcribed as one polycistronic unit together with the open reading frame alr0750. The second cluster, containing hoxU, hoxY, and hoxH, is transcribed together with alr0763 and alr0765, located between the hox genes. Moreover, alr0760 and alr0761 form an additional larger operon. Nevertheless, Northern blot hybridizations revealed a rather complex transcription pattern in which the different hox genes are expressed differently. Transcriptional start points (TSPs) were identified 66 and 57 bp upstream from the start codon of alr0750 and hoxU, respectively. The transcriptions of the two clusters containing the hox genes are both induced under anaerobic conditions concomitantly with the induction of a higher level of hydrogenase activity. An additional TSP, within the annotated alr0760, 244 bp downstream from the suggested translation start codon, was identified. Electrophoretic mobility shift assays with purified LexA from Nostoc sp. strain PCC 7120 demonstrated specific interactions between the transcriptional regulator and both hox promoter regions. However, when LexA from Synechocystis sp. strain PCC 6803 was used, the purified protein interacted only with the promoter region of the alr0750-hoxE-hoxF operon. A search of the whole Nostoc sp. strain PCC 7120 genome demonstrated the presence of 216 putative LexA binding sites in total, including recA and recF. This indicates that, in addition to the bidirectional hydrogenase gene, a number of other genes, including open reading frames connected to DNA replication, recombination, and repair, may be part of the LexA regulatory network in Nostoc sp. strain PCC 7120.
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Zhang, Huixian, Vydianathan Ravi, Boon-Hui Tay, Sumanty Tohari, Nisha E. Pillai, Aravind Prasad, Qiang Lin, Sydney Brenner et Byrappa Venkatesh. « Lampreys, the jawless vertebrates, contain only two ParaHox gene clusters ». Proceedings of the National Academy of Sciences 114, no 34 (7 août 2017) : 9146–51. http://dx.doi.org/10.1073/pnas.1704457114.

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ParaHox genes (Gsx, Pdx, and Cdx) are an ancient family of developmental genes closely related to the Hox genes. They play critical roles in the patterning of brain and gut. The basal chordate, amphioxus, contains a single ParaHox cluster comprising one member of each family, whereas nonteleost jawed vertebrates contain four ParaHox genomic loci with six or seven ParaHox genes. Teleosts, which have experienced an additional whole-genome duplication, contain six ParaHox genomic loci with six ParaHox genes. Jawless vertebrates, represented by lampreys and hagfish, are the most ancient group of vertebrates and are crucial for understanding the origin and evolution of vertebrate gene families. We have previously shown that lampreys contain six Hox gene loci. Here we report that lampreys contain only two ParaHox gene clusters (designated as α- and β-clusters) bearing five ParaHox genes (Gsxα, Pdxα, Cdxα, Gsxβ, and Cdxβ). The order and orientation of the three genes in the α-cluster are identical to that of the single cluster in amphioxus. However, the orientation of Gsxβ in the β-cluster is inverted. Interestingly, Gsxβ is expressed in the eye, unlike its homologs in jawed vertebrates, which are expressed mainly in the brain. The lamprey Pdxα is expressed in the pancreas similar to jawed vertebrate Pdx genes, indicating that the pancreatic expression of Pdx was acquired before the divergence of jawless and jawed vertebrate lineages. It is likely that the lamprey Pdxα plays a crucial role in pancreas specification and insulin production similar to the Pdx of jawed vertebrates.
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Paço, Ana, Simone Aparecida de Bessa Garcia, Joana Leitão Castro, Ana Rita Costa-Pinto et Renata Freitas. « Roles of the HOX Proteins in Cancer Invasion and Metastasis ». Cancers 13, no 1 (22 décembre 2020) : 10. http://dx.doi.org/10.3390/cancers13010010.

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Invasion and metastasis correspond to the foremost cause of cancer-related death, and the molecular networks behind these two processes are extremely complex and dependent on the intra- and extracellular conditions along with the prime of the premetastatic niche. Currently, several studies suggest an association between the levels of HOX genes expression and cancer cell invasion and metastasis, which favour the formation of novel tumour masses. The deregulation of HOX genes by HMGA2/TET1 signalling and the regulatory effect of noncoding RNAs generated by the HOX loci can also promote invasion and metastasis, interfering with the expression of HOX genes or other genes relevant to these processes. In this review, we present five molecular mechanisms of HOX deregulation by which the HOX clusters products may affect invasion and metastatic processes in solid tumours.
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Wittmann, C., O. Bossinger, B. Goldstein, M. Fleischmann, R. Kohler, K. Brunschwig, H. Tobler et F. Muller. « The expression of the C. elegans labial-like Hox gene ceh-13 during early embryogenesis relies on cell fate and on anteroposterior cell polarity ». Development 124, no 21 (1 novembre 1997) : 4193–200. http://dx.doi.org/10.1242/dev.124.21.4193.

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Clusters of homeobox-containing HOM-C/hox genes determine the morphology of animal body plans and body parts and are thought to mediate positional information. Here, we describe the onset of embryonic expression of ceh-13, the Caenorhabditis elegans orthologue of the Drosophila labial gene, which is the earliest gene of the C. elegans Hox gene cluster to be activated in C. elegans development. At the beginning of gastrulation, ceh-13 is asymmetrically expressed in posterior daughters of anteroposterior divisions, first in the posterior daughter of the intestinal precursor cell E and then in all posterior daughters of the AB descendants ABxxx. In this paper, we present evidence that supports position-independent activation of ceh-13 during early C. elegans embryogenesis, which integrates cell fate determinants and cell polarity cues. Our findings imply that mechanisms other than cell-extrinsic anteroposterior positional signals play an important role in the activation and regulation of the C. elegans Hox gene ceh-13.
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Soshnikova, Natalia, Romain Dewaele, Philippe Janvier, Robb Krumlauf et Denis Duboule. « Duplications of hox gene clusters and the emergence of vertebrates ». Developmental Biology 378, no 2 (juin 2013) : 194–99. http://dx.doi.org/10.1016/j.ydbio.2013.03.004.

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Santini, S. « Evolutionary Conservation of Regulatory Elements in Vertebrate Hox Gene Clusters ». Genome Research 13, no 6 (12 mai 2003) : 1111–22. http://dx.doi.org/10.1101/gr.700503.

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Papageorgiou, Spyros. « Pulling forces acting on Hox gene clusters cause expression collinearity ». International Journal of Developmental Biology 50, no 2-3 (2006) : 301–8. http://dx.doi.org/10.1387/ijdb.052034sp.

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Garcia-Barceló, M. M., X. Miao, V. C. H. Lui, M. T. So, E. S. W. Ngan, T. Y. Y. Leon, D. K. C. Lau et al. « Correlation Between Genetic Variations in Hox Clusters and Hirschsprung's Disease ». Annals of Human Genetics 71, no 4 (2 février 2007) : 526–36. http://dx.doi.org/10.1111/j.1469-1809.2007.00347.x.

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Prin, Fabrice, Patricia Serpente, Nobue Itasaki, Yan Gu, Donald M. Bell et Alex P. Gould. « 03-P021 Live imaging of Hox-induced neuroepithelial cell clusters ». Mechanisms of Development 126 (août 2009) : S73. http://dx.doi.org/10.1016/j.mod.2009.06.074.

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