Vezf1 protein binding sites genome-wide are associated with pausing of elongating RNA polymerase II
10.1073/pnas.1121538109
Crossref journal-article
Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences (341)
Abstract

The protein Vezf1 plays multiple roles important for embryonic development. In Vezf1−/−mouse embryonic stem (mES) cells, our earlier data showed widespread changes in gene-expression profiles, including decreased expression of the full-length active isoform of Dnmt3b methyltransferase and concomitant genome-wide reduction in DNA methylation. Here we show that in HeLaS3 cells there is a strong genome-wide correlation between Vezf1 binding and peaks of elongating Ser2-P RNA polymerase (Pol) ll, reflecting Vezf1-dependent slowing of elongation. In WT mES cells, the elongating form of RNA pol II accumulates near Vezf1 binding sites within thednmt3bgene and at several other Vezf1 sites, and this accumulation is significantly reduced at these sites inVezf1−/−mES cells. Depending upon genomic location, Vezf1-mediated Pol II pausing can have different regulatory roles in transcription and splicing. We find examples of genes in which Vezf1 binding sites are located near cassette exons, and in which loss of Vezf1 leads to a change in the relative abundance of alternatively spliced messages. We further show that Vezf1 interacts with Mrg15/Mrgbp, a protein that recognizes H3K36 trimethylation, consistent with the role of histone modifications at alternatively spliced sites.

Bibliography

Gowher, H., Brick, K., Camerini-Otero, R. D., & Felsenfeld, G. (2012). Vezf1 protein binding sites genome-wide are associated with pausing of elongating RNA polymerase II. Proceedings of the National Academy of Sciences, 109(7), 2370–2375.

Authors 4
  1. Humaira Gowher (first)
  2. Kevin Brick (additional)
  3. R. Daniel Camerini-Otero (additional)
  4. Gary Felsenfeld (additional)
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Dates
Type When
Created 13 years, 6 months ago (Jan. 31, 2012, 1:24 a.m.)
Deposited 1 year, 4 months ago (April 18, 2024, 1:57 p.m.)
Indexed 3 months, 3 weeks ago (May 1, 2025, 9:03 a.m.)
Issued 13 years, 6 months ago (Jan. 30, 2012)
Published 13 years, 6 months ago (Jan. 30, 2012)
Published Online 13 years, 6 months ago (Jan. 30, 2012)
Published Print 13 years, 6 months ago (Feb. 14, 2012)
Funders 0

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@article{Gowher_2012, title={Vezf1 protein binding sites genome-wide are associated with pausing of elongating RNA polymerase II}, volume={109}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1121538109}, DOI={10.1073/pnas.1121538109}, number={7}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Gowher, Humaira and Brick, Kevin and Camerini-Otero, R. Daniel and Felsenfeld, Gary}, year={2012}, month=jan, pages={2370–2375} }