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1

Huska, Matthew R. [Verfasser]. "Using Machine Learning to Predict and Better Understand DNA Methylation and Genomic Enhancers / Matthew R. Huska." Berlin : Freie Universität Berlin, 2018. http://d-nb.info/1153007991/34.

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2

Bower, Edward Kenneth Merrick. "The evolution of restriction-modification systems." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/29528.

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Restriction Modification (R-M) systems prevent the invasion of foreign genetic material into bacterial cells and are therefore important in maintaining the integrity of the host genome. The spread of antibiotic resistance, which is proposed to occur via the transfer of foreign genes to the bacterial genome, makes the subject of R-M systems extremely relevant. R-M systems are currently classified into four types (I to IV) on the basis of differences in composition, target recognition, cofactors and the manner in which they cleave DNA. Kennaway et al (2012) proposed that there is an evolutionary
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3

MANIACI, MARIANNA. "THE ROLE OF PROTEIN ARGININE METHYLATION IN RBP-RNA INTERACTION MODULATION AND ITS IMPLICATIONS IN CANCER STRESS RESPONSE INVESTIGATED BY MS-PROTEOMICS." Doctoral thesis, Università degli Studi di Milano, 2022. https://hdl.handle.net/2434/946398.

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Various post-translational modifications (PTMs) have been described to regulate RNA-binding protein (RBP) activity, subcellular localization, and interactions with other proteins or RNAs. Proteome-wide experiments recently carried out in our group have shown that RBPs are the most abundant arginine (R)-methylated proteins. Protein Arginine Methyltransferases (PRMTs) are the enzymes responsible for the deposition of methylation on arginine. Recent evidence has indicated that R-hypomethylation could influence RBP phase-separation and consequent formation of Membrane-Less Organelles (MLOs). In my
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4

MacLeod, A. Robert (Robert Alan) 1966. "DNA methylation and oncogenesis." Thesis, McGill University, 1995. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=39956.

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DNA methylation is a postreplicative covalent modification of the DNA which is catalysed by the DNA methyltransferase enzyme. DNA methylation plays an important role in controlling the gene expression profile of mammalian cells. The hypothesis presented in this thesis is that the expression of the DNA methyltransferase gene is upregulated by cellular oncogenic pathways, and that this induction of MeTase activity results in DNA hypermethylation and plays a causal role in cellular transformation. Novel DNA methyltransferase inhibitors may inhibit the excessive activity of DNA methyltransferase i
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5

Tavares, de Araujo Felipe. "DNA replication and methylation." Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=37847.

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One of the main questions of modern biology is how our cells interpret our genetic and epigenetic information. DNA methylation is a covalent modification of the genome that is essential for mammalian development and plays an important role in the control of gene expression, genomic imprinting and X-chromosome inactivation (Bird and Wolffe, 1999; Szyf et al., 2000). Furthermore, changes in DNA methylation and DNA methyltransferase 1 (DNMT1) activity have been widely documented in a number of human cancers (Szyf, 1998a; Szyf et al., 2000).<br>In Escherichia coli, timing and frequency of initiati
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6

Chik, Pui Chi Flora. "Targeting the DNA methylation machinery in cancers." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=114316.

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Cancer cells have aberrant DNA methylation patterns which are characterized by hypomethylation of a large set of promoters and hypermethylation of tumor suppressor genes. The dynamic nature of the epigenome makes it a valuable target for therapeutic interventions. This thesis focuses on understanding the use of various inhibitors towards DNA methylation-related proteins and their respective anti-cancer activities at both global and gene-specific levels. The widely used demethylating agent 5-azacytidine and 5-aza-2'-deoxycytidine (5-azaCdR) are FDA-approved drugs for the treatment of myelodyspl
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7

Boisvert, François-Michel. "A role for arginine methylation in DNA repair /." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=85887.

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Arginine methylation is a post-translational modification occurring in higher eukaryotes that results in the addition of one or two methyl group on the nitrogen in the side chain of arginines. The enzymes responsible for protein arginine methylation have been classified in three groups. Type I enzymes promote the formation of both NG-monomethylated and asymmetric o-NG,NG-dimethylated arginines (aDMA). Type II enzymes catalyze the formation of monomethylated and symmetrical o-N G,N'G-dimethylated arginines (sDMA). The type III enzyme found in yeast catalyzes the monomethylation of the de
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8

Lucifero, Diana. "Developmental regulation of genomic imprinting by DNA methylation." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=85573.

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Maintaining appropriate patterns of gene expression in the gametes and during early embryogenesis is essential for normal development. DNA methylation is an epigenetic means of regulating gene expression and is an important molecular mark regulating the sex-specific expression of genes subject to genomic imprinting. Imprinted genes are expressed from only one of two inherited chromosomes and are differentially marked during gametogenesis to allow for their parental allele specific expression. These genes affect embryo growth, placental function, behavior after birth and are implicated i
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9

Campbell, Paul Michael. "DNA methylation machinery as molecular targets for cancer therapeutics." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=82836.

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One of the elements commonly seen in cancer is the change in methylation status of the genome. These aberrations in methylation appear to be critical for the neoplastic phenotype and manifest as changes to gene expression of oncogenes and tumour suppressors. In addition to epigenetic alterations, the proteins involved in maintaining the plastic methylation status of the genome, DNA methyltransferases and demethylases, also show methylation-independent protein-protein interactions that have effects on cell cycle progression and proliferation. As changes in gene expression and mitotic reg
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10

Boulanger, Marie-Chloé. "Arginine methylation, the characterization of a post-translational modification." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=85889.

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Proteins are known to be post-translationally modified. This thesis will discuss arginine methylation, one of the many post-translational modifications that occur within the cell. The enzymes that catalyze this post-translational modification are called arginine methyltransferases. The three main types of methylated arginines include monomethylated arginine (MMA), asymmetric dimethylated arginine (aDMA) and symmetric dimethylated arginines (sDMA). Type I arginine methyltransferases catalyze the formation of MMA and aDMA; Type II enzyme catalyze the formation of MMA and sDMA. Protein arg
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11

Slack, Andrew. "Roles of the DNA methylation machinery in cellular transformation and tumorigenesis." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=37840.

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DNA methylation is vital in genome functions as diverse as parental imprinting, X chromosome inactivation, regulation of gene expression and precipitation of inactive chromatin structures. A growing line of evidence suggests that aberrations in proper homeostatic regulation of genomic methylation status are causal in oncogenic processes. Recent evidence has also revealed novel roles of the DNA Methyltransferase (DNMT1), the enzyme believed to be largely responsible for maintenance of the DNA methylation pattern, in replication and in direct regulation of chromatin structure which may help to e
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12

Detich, Nancy. "Regulation of the DNA methylation machinery and its role in epigenetic control." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=19406.

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A growing line of evidence indicates that the proper control of DNA methyltransferases (DNMT) and DNA demethylases is critical for maintaining correct gene expression. In addition, misregulation of this machinery likely plays a role in the aberrant DNA methylation patterns and gene expression that is a hallmark of many pathologies such as cancer. A greater comprehension of the mechanisms involved in regulating the expression and activity of these proteins should provide new therapies aimed at restoring gene expression gone wrong.
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13

Siu, Vincent. "MGMT promoter methylation and expression in glial tumours and peripheral blood mononuclear cells." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=86563.

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O6-Methylguanine DNA methyltransferase (MGMT) is an inducible DNA repair protein that acts to repair damage by DNA alkylating agents currently used in chemotherapy, such as temozolomide. MGMT removes the alkyl group placed at the O6-position of guanine by these alkylating agents, decreasing their efficacy. It has been shown that epigenetic methylation of the O6-MGMT DNA promoter region in tumour tissue from glioblastoma multiforme (GBM) is associated with improved survival from patients treated with temozolomide and concomitant radiotherapy. We wanted to assess the levels of MGMT promoter meth
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14

Wang, Dongsha. "The state of DNA methylation of serotonin transporter (SLC6A4) in peripheral T cells and monocytes is associated with aggression and central 5-HT function; DNA methylation as biomarkers of brain function." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=107671.

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Aggressive behaviour is a complex phenomenon that often arises in early childhood and typically decreases with age. Studies have shown that adults with severe aggression often have lower serotonin (5-HT) neurotransmission. The hypothesis of this thesis is that 5-HT alterations associated with childhood aggression are also defined by epigenetic mechanisms through differential methylation of critical genes in the 5-HT pathway that can be detected in peripheral white blood cells. Serotonin transporter (SLC6A4) was chosen in this study based on its importance in 5-HT function and preliminary genom
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15

Djuric, Ugljesa. "Extent of DNA methylation in biparental hydatidiform moles and functional consequences of NALP7 mutations." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=116066.

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Hydatidiform mole (HM) is an abnormal human pregnancy characterized by cystic degeneration of chorionic villi and absence of embryo. It has been correctly proposed that deregulation of imprinted genes, expressed in a parent-of-origin specific pattern, leads to this pathology due to the fact that biparental and androgenetic HMs are indistinguishable at the phenotypic level. To determine the extent of the abnormal DNA methylation in two biparental moles from a family with a mutation in NALP7, we assessed long interspersed nuclear elements (LINEs), inactive X-linked genes and three tumour suppres
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16

Oakes, Christopher Charles. "DNA methylation in male germ cells : the acquisition and maintenance of unique genome-wide patterns." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=103175.

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The development of healthy gametes is paramount to the health of progeny and to the survival of a species. Epigenetic information contained within gametic DNA in the form of DNA methylation is essential for germ cell and embryo development. DNA methylation is a genome-wide phenomenon involved in the control of gene expression and chromosome structure and stability. During germ line development, patterns of DNA methylation are established in a sex- and sequence-specific manner. The primary goal of the work presented in this thesis is to gain an understanding of the nature of the genome-wide pat
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17

Chénard, Carol Anne. "Ribonucleoprotein complexes and protein arginine methylation : a role in diseases of the central nervous sytem." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=115894.

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For the past 45 years, QKI has been studied for its role in the processes of development and central nervous system myelination using the qkv mouse. The presence of a single KH domain and the recent identification of a high-affinity binding site in mRNAs, suggests that it can bind to and regulate mRNAs through processes such as stability, splicing and transport. As a member of the STAR RNA binding family of proteins the QKI isoforms may also be involved in cell signaling pathways.<br>QKI's involvement in all of these processes, lead us to examine both the protein partners and the mRNA targets
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18

Labonté, Benoit. "The epigenetics of suicide: the impact of early-life adversity on brain DNA methylation signature." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=117086.

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Suicide is a problem resulting from the interaction between several factors. Among these factors, early-life adversity, characterized by child sexual and physical abuse as well as parental neglect, is one of the strongest risk factors for depression and suicidal behaviors. While it is clear that child abuse increases the risk for depression and suicide, the mechanisms mediating these effects are still unknown. Recent evidences suggest that epigenetic mechanisms may be involved in mediating the effects of early-life adversity on behavior. Early-life stress in animals has been shown to alter DNA
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19

Niles, Kirsten Marijke. "The acquisition, dynamics, and perturbation of DNA methylation in the prenatal and early postnatal male germline." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=107573.

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DNA methylation is an epigenetic modification that is essential for germline and embryo development. DNA methylation establishment occurs in the germline in a gender and site specific manner through the action of DNA cytosine-5-methyltransferase (DNMT) enzymes. Spermatozoa have been shown to have a unique configuration of DNA methylation as compared to somatic cells. Germline DNA methylation may also depend on the availability of methyl donors provided by the folate pathway through the action of 5,10-methylenetetrahydrofolate reductase (MTHFR). Absence of MTHFR has been associated with methyla
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20

Wang, Xiaoliang 1980. "DNA methylation of two milk protein genes in lactating and non-lactating bovine mammary gland tissues." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=116076.

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It is well known that DNA methylation in gene promoter regions inhibits gene transcription and that tissue-specific gene expression is partially under the control of this transcription regulatory mechanism. In this study, bovine mammary gland tissues were collected from individual animals in lactating and non-lactating stages to investigate the DNA methylation patterns in the kappa-casein gene and alpha-lactalbumin gene core promoter regions using the bisulphite treatment in combination with polymerase chain reaction (PCR) sequencing. Different methylation status of each sample was classified
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21

Barker, Sharon. "The intracellular localization of mammalian DNA ligase I." Thesis, McGill University, 1996. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=23986.

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DNA replication is cruciaI for the transmission of genetic information. Understanding the enzymology involved in this complex process will allow further insight into its mechanism. Experimental evidence indicates a role for DNA ligase I in DNA replication. Techniques of molecular and cellular biology and immunology were utilized in this study to further investigate DNA ligase I and clarify its involvement and interaction with other proteins in DNA replication. Immunofluorescence studies were performed to examine the intracellular distribution of DNA ligase I. Confocal analysis of indirect immu
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22

Huynh, The Hung. "The role of DNA methylation in the regulation of bovine B-casein and a-lactalbumin gene expression." Thesis, McGill University, 1994. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=28784.

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DNA methylation has been shown to be involved in switching a number of genes on or off in particular cells. The relationship between DNA methylation and $ beta$-casein gene expression in the mammary tissue of lactating cows and mammary epithelial cells was examined. A positive correlation existed between hypomethylation of two MspI/HpaII sites in the body and one MspI/HpaII site in the 3$ sp prime$ end of the $ beta$-casein gene and its expression. In addition to these sites, hypomethylation of a distal MspI/HpaII site and HindIII sensitivity at a HindIII site also correlated with gene express
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23

Checknita, David. "Monoamine oxidase A gene promoter methylation and impulsive aggression in an offender population with antisocial personality disorder." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=121478.

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Antisocial personality disorder (ASPD) is a condition characterized by elevated impulsive aggression and increased risk for criminal behaviour and incarceration. Deficient activity of the monoamine oxidase A (MAOA) gene is suggested to contribute to serotonergic system dysregulation strongly associated with impulsive aggression and ASPD. The potential contribution of epigenetic processes, which modulate gene expression without altering the underlying genomic code, towards the dysregulation of MAOA in ASPD is not yet understood.The current study aimed to elucidate the role of epigenetic process
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24

Ghorayeb, Yasmine. "Combined effects of superovulation and decreased levels of DNA methyltransferase 1O on imprinted gene methylation in preimplantation embryos." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=119651.

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Recent studies indicate that children conceived using assisted reproductive technologies are at increased risk of growth disorders and genomic imprinting diseases. Reports have suggested that these disorders could result from epimutations including abnormal DNA methylation patterns in imprinted genes. DNA methylation, catalyzed by a family of DNA methyltransferases (DNMTs), is both heritable and reversible and is the major epigenetic mark associated with imprinting. We propose that techniques used in ART, such as ovarian stimulation, and factors underlying infertility might interact to disrupt
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25

Kelly, Tamara Lee Jocelyn. "Pharmacological and genetic approaches to altering DNA methylation in the mouse male germ line : effects on spermatogenesis and embryogenesis." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=85923.

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DNA methylation is an epigenetic phenomenon catalysed by a family of DNA methyltransferases (DNMTs) and is tightly regulated throughout spermatogenesis. In these studies, I employed pharmacological and genetic means to disrupt DNA methylation in the male germ line. First, to lower levels of DNMT activity, I treated adult wild-type (Dnmt1+/+) and DNMT-deficient (Dnmt1c/+) male mice with the anticancer agent 5-aza-2'-deoxycytidine (5-azaCdR), which incorporates into DNA and inhibits methylation. Dnmt1+/+ males treated with clinical doses of 5-azaCdR for 7 weeks, to expose germ cells throu
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26

Garner, Justine. "The effects of 5,10-Methylenetetrahydrofolate Reductase deficiency and Methionine supplementation on the DNA Methylation patterns of early male germ cells." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=110667.

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Improper acquisition of DNA methylation patterns during the fetal period in germ cells of male mice is associated with impaired meiosis and infertility. MTHFR is a key folate pathway enzyme involved in providing methyl groups for DNA methylation. The goal of these studies was to evaluate DNA methylation patterns in spermatogonia from mice heterozygous for a targeted deletion in Mthfr (Mthfr+/-) as compared to those of their wildtype, Mthfr+/+, littermates. DNA methylation patterns were similar at imprinted genes and intergenic sites across chromosome 9 in neonatal spermatogonia of Mthfr+/+ and
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27

La, Salle Sophie. "Origin of DNA methylation patterns in the male germ line : roles of the novel DNA methyltransferases in male germ cells." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=103166.

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Formation of gametes capable of supporting development is dependent on a number of genetic and epigenetic events. DNA methylation is an epigenetic modification catalyzed by enzymes named DNA methyltransferases (DNMTs). In the mouse, methylation of DNA is associated with the control of gene expression and proper embryo development. Methylation patterns are established in a sex- and sequence-specific manner during male and female germ cell development and further modified during early embryonic development. Even though new DNMTs have recently been identified, little information is known on the o
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28

Saint-Phar, Shawna. "Development and characterization of a mouse model to determine the impact of low dietary folate on spermatogenesis, fertility and histone methylation." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=32416.

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Folate is a critical determinant in male reproductive health. During spermatogenesis, there are massive alterations to the epigenome associated with tightly regulated gene transcription and chromatin reorganization including a tightly regulated pattern of histone H3 methylation. In vitro experiments were conducted to determine whether folate depletion could alter global histone H3 methylation at lysine 4 and 9 in cultured spermatogonia-like GC-1 cells. Folate depleted media did not alter global levels of
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29

Farag, Mena. "The role of DNA-methyltransferase 3-like (DNMT3L) in the establishment and stability of DNA Methylation patterns in the male germline." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=116966.

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The enzyme DNA methyltransferase 3-like (DNMT3L) is essential for de novo DNA methylation in germ cells, proper germ cell development, and has been reported as the first paternal effect gene in mammals. In mice, although Dnmt3L heterozygous or haploinsufficient (+/-) males are fertile, there are associated chromosomal compaction abnormalities and the males have been shown to sire an increased number of aneuploid offspring even if the offspring do not possess the mutant allele (the paternal effect). Despite this, there have been no reported DNA methylation abnormalities in Dnmt3L haploinsuffic
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30

"Mechanistic study of the effect of CDH1 promoter hypermethylation on drug resistance and related gene expression in multidrug resistant human hepatocellular carcinoma R-HepG2 cells." Thesis, 2010. http://library.cuhk.edu.hk/record=b6075035.

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"Epigenetic" refers to a heritable change in the gene expression pattern that is not mediated by any alterations in the primary nucleotide sequence of a gene in the genome. This change involves methylation of DNA in the gene promoter regions, modification of histone residues and chromatin remodeling. Among them, methylation of DNA promoter region is an essential step in epigenetic gene silencing and is known to be closely related to carcinogenesis and cancer progression.<br>Our preliminary study on effect of treatments of some potential anti-cancer drug candidates, namely Pheophorbide A (Pa),
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