The n-SET domain of Set1 regulates H2B ubiquitylation-dependent H3K4 methylation

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Title
The n-SET domain of Set1 regulates H2B ubiquitylation-dependent H3K4 methylation
Author(s)
J Kim; Jung Ae Kim; R K McGinty; U T T Nguyen; T W Muir; C D Allis; R G Roeder
Publication Year
2013
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.
ISSN
1097-2765
Publisher
Elsevier (Cell Press)
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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