A phospho/methyl switch at histone H3 regulates TFIID association with mitotic chromosomes

被引：74

作者：

Varier, Radhika A. ^{[1
,2
]}

Outchkourov, Nikolay S. ^{[1
,2
]}

de Graaf, Petra ^{[1
,2
]}

van Schaik, Frederik M. A. ^{[1
,2
]}

Ensing, Henk Jan L. ^{[1
,2
]}

Wang, Fangwei ^{[3
]}

Higgins, Jonathan M. G. ^{[3
]}

Kops, Geert J. P. L. ^{[1
,2
]}

Timmers, H. Th Marc ^{[1
,2
]}

机构：

[1] Univ Med Ctr Utrecht, Dept Physiol Chem, NL-3584 CG Utrecht, Netherlands

[2] Univ Med Ctr Utrecht, Netherlands Prote Ctr, NL-3584 CG Utrecht, Netherlands

[3] Harvard Univ, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Sch Med, Boston, MA 02115 USA

来源：

EMBO JOURNAL | 2010年 / 29卷 / 23期

基金：

美国国家卫生研究院;

关键词：

haspin; histone methylation; mitosis; PHD; TFIID; RNA-POLYMERASE-II; TATA-BINDING PROTEIN; PHD FINGER; TRANSCRIPTION INITIATION; AURORA-B; METHYLTRANSFERASE COMPLEX; LYSINE-4; TRIMETHYLATION; PROMOTER SELECTIVITY; PLANT HOMEODOMAIN; GENE-EXPRESSION;

D O I：

10.1038/emboj.2010.261

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. The EMBO Journal (2010) 29, 3967-3978. doi:10.1038/emboj.2010.261; Published online 15 October 2010

引用

页码：3967 / 3978

页数：12

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