Dnmt3a-Dependent Nonpromoter DNA Methylation Facilitates Transcription of Neurogenic Genes
This paper showed that Dnmt3a can methylate both promoter and non-promoter DNA regions, with the latter being transcriptionally permissive. Dnmt3a antagonizes Polycomb complex binding and thus the silencing impact by H3K27me3 on transcription. Further, the authors suggested Polycomb may help recruit Dnmt via their direct interaction, and eventually Dnmt activity would be sufficient to counteract the repression by Polycomb. It should be very helpful to pursue how the regulation is coordinated on different genes and during different developmental processes.
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This paper does a good job of showing how Dnmt3a and DNA methylation is linked to postnatal neurogenesis. The primary question that arose to me after studying figure 1 was how is DNA methylation needed/related to neuronal differentiation. They seem to address this fundamental question with ChIP on chip and find that H3k4 tri-methylation coorelates with Dnmt3a target genes involved in neurogenesis. They also show how DNA methylation with in or flanking the proximal promoter can repress or promote gene transcription. It would be interesting to look at how DNA methylation and Dnmt3a is altered in neurological disorders and cancers.
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