title: The n-SET domain of Set1 regulates H2B ubiquitylation-dependent H3K4 methylation.
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.
authors: Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA.
authors: Jaehoon
authors: J
authors: Kim
authors: Jung-Ae
authors: JA
authors: Kim
authors: Robert K
authors: RK
authors: McGinty
authors: Uyen T T
authors: UT
authors: Nguyen
authors: Tom W
authors: TW
authors: Muir
authors: C David
authors: CD
authors: Allis
authors: Robert G
authors: RG
authors: Roeder
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D002843:Chromatin / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry; D006367:HeLa Cells; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry*; D006657:Histones / Q000737:chemistry*; D006801:Humans; D008745:Methylation; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021122:Protein Subunits / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D061987:Sf9 Cells; D018411:Spodoptera; D054875:Ubiquitination; D029867:Xenopus Proteins / Q000737:chemistry
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D046912:Multiprotein Complexes; D021122:Protein Subunits; C524367:SPP1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D029867:Xenopus Proteins; D011495:Histone-Lysine N-Methyltransferase; C411250:SET1 protein, S cerevisiae