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A phospho/methyl switch at histone H3 regulates TFIID association with mitotic chromosomes
Author(s) -
Varier Radhika A,
Outchkourov Nikolay S,
de Graaf Petra,
van Schaik Frederik M A,
Ensing Henk Jan L,
Wang Fangwei,
Higgins Jonathan M G,
Kops Geert J P L,
Timmers HTh Marc
Publication year - 2010
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2010.261
Subject(s) - biology , histone h3 , genetics , mitosis , microbiology and biotechnology , histone , dna
Histone methylation patterns are correlated with eukaryotic gene transcription. High‐affinity binding of the plant homeodomain (PHD) of TFIID subunit TAF3 to trimethylated lysine‐4 of histone H3 (H3K4me3) is involved in promoter recruitment of this basal transcription factor. Here, we show that for transcription activation the PHD of TAF3 can be replaced by PHDs of other high‐affinity H3K4me3 binders. Interestingly, H3K4me3 binding of TFIID and the TAF3‐PHD is decreased by phosphorylation of the adjacent threonine residue (H3T3), which coincides with mitotic inhibition of transcription. Ectopic expression of the H3T3 kinase haspin repressed TAF3‐mediated transcription of endogenous and of reporter genes and decreased TFIID association with chromatin. Conversely, immunofluorescence and live‐cell microscopy studies showed an increased association of TFIID with mitotic chromosomes upon haspin knockdown. Based on our observations, we propose that a histone H3 phospho–methyl switch regulates TFIID‐mediated transcription during mitotic progression of the cell cycle.