[Seminar] "New Roles of Maintenance Methylation Factors DNMT1 and NP95/UHRF1 for Chromatin Mediated Transcriptional Regulation" by Dr. Sharif Jafar
Speaker: Dr. Jafar Sarif, RIKEN IMS, Yokohama Japan
Title: New Roles of Maintenance Methylation Factors DNMT1 and NP95/UHRF1 for Chromatin Mediated Transcriptional Regulation
In mammals, transcriptional silencing is mediated by DNA (5-cytosine) methylation, as well as repressive chromatin marks such as histone H3 lysine 9 tri-methylation (H3K9me3) and histone H3 lysine 27 tri-methylation (H3K27me3). DNMT1 (DNA methyltransferase 1) and NP95 (Nuclear Protein 95 kDa, also known as UHRF1) are key players for maintenance of DNA methylation in mammalian cells (Sharif et al, 2007; Nishiyama et al, 2013). Interestingly, from recent studies it is gradually becoming clear that DNMT1 and NP95 do more than just maintenance of DNA methylation. Indeed, we have recently shown that in cells that are undergoing passive loss of DNA methylation, NP95 binds to ectopic hemimethylated DNA (DNA methylation in only one strand of the CpG dyad) and inhibits accumulation of H3K9me3, thereby promoting transcriptional activation (Sharif et al, 2016). Furthermore, our preliminary analysis indicates a function of DNMT1 to mediate H3K27me3-dependent gene silencing. Intriguingly, this function appears to be independent of the DNA methylase activity of DNMT1. In my talk, I will discuss these recent findings, and argue that DNMT1 and NP95 play a broader role to control mammalian epigenetics that extends beyond their previously annotated function in maintenance DNA methylation.