Histone Crosstalk between H2B Monoubiquitination and H3 Methylation Mediated by COMPASS

Jung Shin Lee, Abhijit Shukla, Jessica Schneider, Selene K. Swanson, Michael P. Washburn, Laurence Florens, Sukesh R. Bhaumik, Ali Shilatifard*

*Corresponding author for this work

Research output: Contribution to journalArticle

286 Scopus citations

Abstract

COMPASS, the yeast homolog of the mammalian MLL complex, is a histone H3 lysine 4 (H3K4) methylase consisting of Set1 (KMT2) and seven other polypeptides, including Cps35, the only essential subunit. Histone H2B monoubiquitination by Rad6/Bre1 is required for both H3K4 methylation by COMPASS, and H3K79 methylation by Dot1. However, the molecular mechanism for such histone crosstalk is poorly understood. Here, we demonstrate that histone H2B monoubiquitination controls the binding of Cps35 with COMPASS complex. Cps 35 is required for COMPASS' catalytic activity in vivo, and the addition of exogenous purified Cps35 to COMPASS purified from a Δrad6 background results in the generation of a methylation competent COMPASS. Cps35 associates with the chromatin of COMPASS-regulated genes in a H2BK123 monoubiquitination-dependent but Set1-independent manner. Cps35 is also required for proper H3K79 trimethylation. These findings offer insight into the molecular role of Cps35 in translating the H2B monoubiquitination signal into H3 methylation.

Original languageEnglish (US)
Pages (from-to)1084-1096
Number of pages13
JournalCell
Volume131
Issue number6
DOIs
StatePublished - Dec 14 2007

Keywords

  • DNA
  • PROTEINS

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Lee, J. S., Shukla, A., Schneider, J., Swanson, S. K., Washburn, M. P., Florens, L., Bhaumik, S. R., & Shilatifard, A. (2007). Histone Crosstalk between H2B Monoubiquitination and H3 Methylation Mediated by COMPASS. Cell, 131(6), 1084-1096. https://doi.org/10.1016/j.cell.2007.09.046