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SUMMARY:The Regulation of DNA Methylation in Mammalian Development and Can
 cer - Dr Nicolas Veland\; The University of Texas\, MD Anderson Cancer Cen
 ter\, Department of Epigenetics and Molecular Carcinogenesis 
DTSTART:20180529T100000Z
DTEND:20180529T110000Z
UID:TALK106510@talks.cam.ac.uk
CONTACT:Bobbie Claxton
DESCRIPTION:DNA methylation is an essential epigenetic modification in mam
 mals\, as it plays important regulatory roles in multiple biological proce
 sses\, such as gene transcription\, maintenance of chromosomal structure a
 nd genomic stability\, genomic imprinting\, retrotransposon silencing\, an
 d X-chromosome inactivation. Dysregulation of DNA methylation is associate
 d with various human diseases\, including cancer. For example\, cancer cel
 ls usually show global DNA hypomethylation and regional DNA hypermethylati
 on\, which have been implicated in genomic instability and tumor suppresso
 r silencing\, respectively. Although great progress has been made in eluci
 dating the biological functions of DNA methylation over the last several d
 ecades\, how DNA methylation patterns and levels are regulated and dysregu
 lated is not well understood. Using mouse embryonic stem cells (mESCs)\, a
 n ideal model system for studying DNA methylation\, I have discovered nove
 l regulatory mechanisms that play important roles in de novo and maintenan
 ce DNA methylation. In one project\, I show that Dnmt3L\, a key regulator 
 of de novo DNA methylation\, facilitates Dnmt3a-mediated methylation by st
 abilizing Dnmt3a2\, the major Dnmt3a isoform in mESCs\, thus uncovering a 
 new role for Dnmt3L and providing a plausible explanation for the function
 al specificity of Dnmt3L in vivo and for the reproductive phenotypes obser
 ved in genetic mouse models. In a separate project\, I demonstrate that PR
 MT6\, an arginine methyltransferase responsible for asymmetric dimethylati
 on of histone H3 arginine 2 (H3R2me2a)\, negatively regulates maintenance 
 DNA methylation by impairing the recruitment of the Dnmt1-Uhrf1 complex to
  chromatin\, thereby identifying a novel crosstalk between histone arginin
 e methylation and DNA methylation. Moreover\, I show that PRMT6 upregulati
 on contributes to global DNA hypomethylation in cancer. In summary\, the r
 esearch work in this talk advances our understanding of the regulatory net
 work that controls DNA methylation changes in normal developmental process
 es and pathological conditions.
LOCATION:Babraham - The Cambridge Building\; Kings Hedges Room
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