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

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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.
Publisher
CELL PRESS
Issue Date
2013-03
Language
English
Article Type
Article
Keywords

MIXED LINEAGE LEUKEMIA; HISTONE METHYLTRANSFERASE COMPLEX; SACCHAROMYCES-CEREVISIAE; LYSINE-4 METHYLATION; TRANSCRIPTION TERMINATION; ACTIVE GENES; UBIQUITINATION; PROTEIN; TRIMETHYLATION; COMPASS

Citation

MOLECULAR CELL, v.49, no.6, pp.1121 - 1133

ISSN
1097-2765
DOI
10.1016/j.molcel.2013.01.034
URI
http://hdl.handle.net/10203/255073
Appears in Collection
BS-Journal Papers(저널논문)
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