Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex

Michael Christopher Keogh, Siavash K. Kurdistani, Stephanie A. Morris, Seong Hoon Ahn, Vladimir Podolny, Sean R. Collins, Maya Schuldiner, Kayu Chin, Thanuja Punna, Natalie J. Thompson, Charles Boone, Andrew Emili, Jonathan S. Weissman, Timothy R. Hughes, Brian D. Strahl, Michael Grunstein, Jack F. Greenblatt, Stephen Buratowski, Nevan J. Krogan

Research output: Contribution to journalArticle

551 Scopus citations

Abstract

The yeast histone deacetylase Rpd3 can be recruited to promoters to repress transcription initiation. Biochemical, genetic, and gene-expression analyses show that Rpd3 exists in two distinct complexes. The smaller complex, Rpd3C(S), shares Sin3 and Ume1 with Rpd3C(L) but contains the unique subunits Rco1 and Eaf3. Rpd3C(S) mutants exhibit phenotypes remarkably similar to those of Set2, a histone methyltransferase associated with elongating RNA polymerase II. Chromatin immunoprecipitation and biochemical experiments indicate that the chromodomain of Eaf3 recruits Rpd3C(S) to nucleosomes methylated by Set2 on histone H3 lysine 36, leading to deacetylation of transcribed regions. This pathway apparently acts to negatively regulate transcription because deleting the genes for Set2 or Rpd3C(S) bypasses the requirement for the positive elongation factor Bur1/Bur2.

Original languageEnglish (US)
Pages (from-to)593-605
Number of pages13
JournalCell
Volume123
Issue number4
DOIs
StatePublished - Nov 18 2005

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Keogh, M. C., Kurdistani, S. K., Morris, S. A., Ahn, S. H., Podolny, V., Collins, S. R., Schuldiner, M., Chin, K., Punna, T., Thompson, N. J., Boone, C., Emili, A., Weissman, J. S., Hughes, T. R., Strahl, B. D., Grunstein, M., Greenblatt, J. F., Buratowski, S., & Krogan, N. J. (2005). Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex. Cell, 123(4), 593-605. https://doi.org/10.1016/j.cell.2005.10.025