Chromatin Binding of SRp20 and ASF/SF2 and Dissociation from Mitotic Chromosomes Is Modulated by Histone H3 Serine 10 Phosphorylation

被引:146
作者
Loomis, Rebecca J. [1 ,2 ]
Naoe, Yoshinori [1 ,2 ]
Parker, J. Brandon [1 ,2 ,3 ]
Savic, Velibor [3 ]
Bozovsky, Matthew R. [1 ,2 ]
Macfarlan, Todd [3 ]
Manley, James L. [4 ]
Chakravarti, Debabrata [1 ,2 ]
机构
[1] Northwestern Univ, Feinberg Sch Med, Div Reprod Biol Res, Dept Obstet & Gynecol, Chicago, IL 60611 USA
[2] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA
[3] Univ Penn, Grad Program Biol Sci, Philadelphia, PA 19104 USA
[4] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA
关键词
SPLICING FACTOR ASF/SF2; SR PROTEINS; FISSION YEAST; CELL-CYCLE; LYSINE; 9; HETEROCHROMATIN; HP1; CONDENSATION; KINASE; RECOGNITION;
D O I
10.1016/j.molcel.2009.02.003
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 H3 serine 10 phosphorylation is a hallmark of mitotic chromosomes, but its full function remains to be elucidated. We report here that two SR protein splicing factors, SRp20 and ASF/SF2, associate with interphase chromatin, are released from hyper-phosphorylated mitotic chromosomes, but reassociate with chromatin late in M-phase. Inhibition of Aurora B kinase diminished histone H3 serine 10 phosphorylation and increased SRp20 and ASH SF2 retention on mitotic chromosomes. Unexpectedly, we also found that HP1 proteins interact with ASF/SF2 in mitotic cells. Strikingly, siRNA-mediated knockdown of ASF/SF2 caused retention of HP1 proteins on mitotic chromatin. Finally, ASF/SF2-depleted cells released from a mitotic block displayed delayed G0/G1 entry, suggesting a functional consequence of these interactions. These findings underscore the evolving role of histone H3 phosphorylation and demonstrate a direct, functional, and histone-modification-regulated association of SRp20 and ASF/SF2 with chromatin.
引用
收藏
页码:450 / 461
页数:12
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