Bgp1/Vezf1 couples RNA Pol II activity and maintenance of genomic methylation

Abstract

The protein Vezf1 plays multiple roles within the nucleus. Vezf1−/− mouse embryonic stem (MES) cells show widespread changes in gene expression profiles, including genome wide reduction in DNA methylation, which can be ascribed to a change in abundance of the RNA splice variant coding for the DNA methyltransferase Dnmt3b. We show here that the elongating form of RNA polymerase II accumulates at a Vezf1 binding site within a Dnmt3b intron in Wt MES cells, but not in Vezf1−/− cells. Vezf1 dependent Pol II pausing was seen at several intragenic and promoter‐associated Vezf1 binding sites in mouse ES cells. We carried out a genome wide ChIP‐seq study in HeLa cells of the distribution of both Vezf1 and Ser2P‐Pol II. There is a strong correlation between Vezf1 binding and peaks in abundance of elongating polymerase. Given the known relationship between RNA elongation rates, pausing, and splice variant choice, these results suggest that Vezf1, when bound at introns, may play a significant role in splicing outcomes.