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

• DOI: 10.1016/j.molcel.2013.01.034
• Publication Date: 2013-02-28T16:32:12Z
• Authors: Jaehoon Kim; Jung-Ae Kim; Robert K. McGinty; Uyen T.T. Nguyen; Tom W. Muir; C. David Allis; Robert G. Roeder
• Keywords: Crosstalk; Histone Methylation; Histone H2B

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.