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.
Mesh Terms:
Amino Acid Motifs, Amino Acid Sequence, Animals, Catalytic Domain, Chromatin, DNA-Binding Proteins, HeLa Cells, Histone-Lysine N-Methyltransferase, Histones, Humans, Methylation, Molecular Sequence Data, Multiprotein Complexes, Protein Binding, Protein Interaction Domains and Motifs, Protein Subunits, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sf9 Cells, Spodoptera, Ubiquitination, Xenopus Proteins
Amino Acid Motifs, Amino Acid Sequence, Animals, Catalytic Domain, Chromatin, DNA-Binding Proteins, HeLa Cells, Histone-Lysine N-Methyltransferase, Histones, Humans, Methylation, Molecular Sequence Data, Multiprotein Complexes, Protein Binding, Protein Interaction Domains and Motifs, Protein Subunits, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sf9 Cells, Spodoptera, Ubiquitination, Xenopus Proteins
Mol. Cell
Date: Mar. 28, 2013
PubMed ID: 23453808
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