The n-SET Domain of Set1 Regulates H2B Ubiquitylation-Dependent H3K4 Methylation

Jaehoon Kim, Jung Ae Kim, Robert K. McGinty, Uyen T.T. Nguyen, Tom W. Muir, C. David Allis, Robert G. Roeder

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

Past studies have documented a crosstalk between H2B ubiquitylation (H2Bub) and H3K4 methylation, but little (if any) direct evidence exists explaining the mechanism underlying H2Bub-dependent H3K4 methylation on chromatin templates. Here, we took advantage of an in vitro histone methyltransferase assay employing a reconstituted yeast Set1 complex (ySet1C) and a recombinant chromatin template containing fully ubiquitylated H2B to gain valuable insights. Combined with genetic analyses, we demonstrate that the n-SET domain within Set1, but not Swd2, is essential for H2Bub-dependent H3K4 methylation. Spp1, a homolog of human CFP1, is conditionally involved in this crosstalk. Our findings extend to the human Set1 complex, underscoring the conserved nature of this disease-relevant crosstalk pathway. As not all members of the H3K4 methyltransferase family contain n-SET domains, our studies draw attention to the n-SET domain as a predictor of an H2B ubiquitylation-sensing mechanism that leads to downstream H3K4 methylation.

Original languageEnglish (US)
Pages (from-to)1121-1133
Number of pages13
JournalMolecular Cell
Volume49
Issue number6
DOIs
StatePublished - Mar 28 2013

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The n-SET Domain of Set1 Regulates H2B Ubiquitylation-Dependent H3K4 Methylation'. Together they form a unique fingerprint.

  • Cite this

    Kim, J., Kim, J. A., McGinty, R. K., Nguyen, U. T. T., Muir, T. W., Allis, C. D., & Roeder, R. G. (2013). The n-SET Domain of Set1 Regulates H2B Ubiquitylation-Dependent H3K4 Methylation. Molecular Cell, 49(6), 1121-1133. https://doi.org/10.1016/j.molcel.2013.01.034