TY - JOUR
T1 - Symmetric dimethylation of H3R2 is a newly identified histone mark that supports euchromatin maintenance
AU - Migliori, Valentina
AU - Müller, Julius
AU - Phalke, Sameer
AU - Low, Diana
AU - Bezzi, Marco
AU - Mok, Wei Chuen
AU - Sahu, Sanjeeb Kumar
AU - Gunaratne, Jayantha
AU - Capasso, Paola
AU - Bassi, Christian
AU - Cecatiello, Valentina
AU - De Marco, Ario
AU - Blackstock, Walter
AU - Kuznetsov, Vladimir
AU - Amati, Bruno
AU - Mapelli, Marina
AU - Guccione, Ernesto
PY - 2012/2
Y1 - 2012/2
N2 - The asymmetric dimethylation of histone H3 arginine 2 (H3R2me2a) acts as a repressive mark that antagonizes trimethylation of H3 lysine 4. Here we report that H3R2 is also symmetrically dimethylated (H3R2me2s) by PRMT5 and PRMT7 and present in euchromatic regions. Profiling of H3-tail interactors by SILAC MS revealed that H3R2me2s excludes binding of RBBP7, a central component of co-repressor complexes Sin3a, NURD and PRC2. Conversely H3R2me2s enhances binding of WDR5, a common component of the coactivator complexes MLL, SET1A, SET1B, NLS1 and ATAC. The interaction of histone H3 with WDR5 distinguishes H3R2me2s from H3R2me2a, which impedes the recruitment of WDR5 to chromatin. The crystallographic structure of WDR5 and the H3R2me2s peptide elucidates the molecular determinants of this high affinity interaction. Our findings identify H3R2me2s as a previously unknown mark that keeps genes poised in euchromatin for transcriptional activation upon cell-cycle withdrawal and differentiation in human cells.
AB - The asymmetric dimethylation of histone H3 arginine 2 (H3R2me2a) acts as a repressive mark that antagonizes trimethylation of H3 lysine 4. Here we report that H3R2 is also symmetrically dimethylated (H3R2me2s) by PRMT5 and PRMT7 and present in euchromatic regions. Profiling of H3-tail interactors by SILAC MS revealed that H3R2me2s excludes binding of RBBP7, a central component of co-repressor complexes Sin3a, NURD and PRC2. Conversely H3R2me2s enhances binding of WDR5, a common component of the coactivator complexes MLL, SET1A, SET1B, NLS1 and ATAC. The interaction of histone H3 with WDR5 distinguishes H3R2me2s from H3R2me2a, which impedes the recruitment of WDR5 to chromatin. The crystallographic structure of WDR5 and the H3R2me2s peptide elucidates the molecular determinants of this high affinity interaction. Our findings identify H3R2me2s as a previously unknown mark that keeps genes poised in euchromatin for transcriptional activation upon cell-cycle withdrawal and differentiation in human cells.
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U2 - 10.1038/nsmb.2209
DO - 10.1038/nsmb.2209
M3 - Article
C2 - 22231400
AN - SCOPUS:84856733701
VL - 19
SP - 136
EP - 145
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
SN - 1545-9993
IS - 2
ER -