A phospho/methyl switch at histone H3 regulates TFIID association with mitotic chromosomes.
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.
Department of Physiological Chemistry and Netherlands Proteomics Center, University Medical Centre Utrecht, Utrecht, The Netherlands.
Radhika A
RA
Varier
Nikolay S
NS
Outchkourov
Petra
P
de Graaf
Frederik M A
FM
van Schaik
Henk Jan L
HJ
Ensing
Fangwei
F
Wang
Jonathan M G
JM
Higgins
Geert J P L
GJ
Kops
H T Marc
HT
Timmers
D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002875:Chromosomes / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008745:Methylation; D008938:Mitosis; D008969:Molecular Sequence Data; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D035362:Transcription Factor TFIID / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
D006657:Histones; D035362:Transcription Factor TFIID; D017346:Protein Serine-Threonine Kinases