TY - JOUR
T1 - Histone H3K27 trimethylation inhibits H3 binding and function of SET1-Like H3K4 methyltransferase complexes
AU - Kim, Dae Hwan
AU - Tang, Zhanyun
AU - Shimada, Miho
AU - Fierz, Beat
AU - Houck-Loomis, Brian
AU - Bar-Dagen, Maya
AU - Lee, Seunghee
AU - Lee, Soo Kyung
AU - Muir, Tom W.
AU - Roeder, Robert G.
AU - Lee, Jae W.
PY - 2013/12
Y1 - 2013/12
N2 - Trimethylated histone H3 lysine 4 (H3K4) and H3K27 generally mark transcriptionally active and repressive chromatins, respectively. In most cell types, these two modifications are mutually exclusive, and this segregation is crucial for the regulation of gene expression. However, how this anticorrelation is achieved has not been fully understood. Here, we show that removal of the H3K27 trimethyl mark facilitates recruitment of SET1-like H3K4 methyltransferase complexes to their target genes by eliciting a novel interaction between histone H3 and two common subunits, WDR5 and RBBP5, of SET1-like complexes. Consistent with this result, H3K27 trimethylation destabilizes interactions of H3 with SET1-like complexes and antagonizes their ability to carry out H3K4 trimethylation of peptide (H3 residues 1 to 36), histone octamer, and mononucleosome substrates. Altogether, our studies reveal that H3K27 trimethylation of histone H3 represses a previously unrecognized interaction between H3 and SET1-like complexes. This provides an important mechanism that directs the anticorrelation between H3K4 and H3K27 trimethylation.
AB - Trimethylated histone H3 lysine 4 (H3K4) and H3K27 generally mark transcriptionally active and repressive chromatins, respectively. In most cell types, these two modifications are mutually exclusive, and this segregation is crucial for the regulation of gene expression. However, how this anticorrelation is achieved has not been fully understood. Here, we show that removal of the H3K27 trimethyl mark facilitates recruitment of SET1-like H3K4 methyltransferase complexes to their target genes by eliciting a novel interaction between histone H3 and two common subunits, WDR5 and RBBP5, of SET1-like complexes. Consistent with this result, H3K27 trimethylation destabilizes interactions of H3 with SET1-like complexes and antagonizes their ability to carry out H3K4 trimethylation of peptide (H3 residues 1 to 36), histone octamer, and mononucleosome substrates. Altogether, our studies reveal that H3K27 trimethylation of histone H3 represses a previously unrecognized interaction between H3 and SET1-like complexes. This provides an important mechanism that directs the anticorrelation between H3K4 and H3K27 trimethylation.
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U2 - 10.1128/MCB.00601-13
DO - 10.1128/MCB.00601-13
M3 - Article
C2 - 24126056
AN - SCOPUS:84893139184
SN - 0270-7306
VL - 33
SP - 4936
EP - 4946
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 24
ER -