||Friday, 20 March 2015, 16:00～
|| Seminar-shitsu 1, IDAC Research building 7F
||The importance of being “half”: An unexpected role of hemimethylated DNA & Np95 for activation of proviral sequences in the placenta
||Jafar Sharif Ph.D.
||Staff Scientist, RIKEN Institute for Integrative Medical Sciences (IMS), Yokohama
||Yasuhisa Matsui Cell Resource Center for Biomedical Research (ex:8571)
||DNA methylation is an essential epigenetic mark in mammals and is thought to be associated with gene silencing; while demethylation has been classically linked with transcriptional activation. In this talk, based on genetic and biochemical analyses performed in DNA methylation mutant mice, I will show that contrary to the present model, transcription can be efficiently silenced despite genomewide acute (DNA) demethylation. Surprisingly, enrichment of hemimethylated DNA (cytosine methylation in only one strand of the CpG dyad) followed by binding of its dedicated reader molecule NP95/UHRF1, gives rise to robust transcription by destabilization of the H3K9me3-SETDB1 repressive pathway. Finally, I will introduce our recent results revealing a biological role for the hemimethylated DNA-NP95 axis to activate proviral (LTR-associated endogenous retrovirus) sequences in the placenta. Hemimethylated DNA and Np95 could thus play a role to regulate transcription, in particular, from the proviral loci, in a developmental stage specific manner.