XB-ART-47166Mol Cell March 28, 2013; 49 (6): 1121-33.
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The n-SET domain of Set1 regulates H2B ubiquitylation-dependent H3K4 methylation.
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.
PubMed ID: 23453808
PMC ID: PMC3615140
Article link: Mol Cell
Species referenced: Xenopus
Genes referenced: h2bc21 wdr82
References [+] :
Briggs, Histone H3 lysine 4 methylation is mediated by Set1 and required for cell growth and rDNA silencing in Saccharomyces cerevisiae. 2001, Pubmed