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

• DOI: 10.1016/j.molcel.2009.02.003
• Publication Date: 2009-02-27T09:28:52Z
• Authors: Rebecca J. Loomis; Yoshinori Naoe; J. Brandon Parker; Velibor Savic; Matthew R. Bozovsky; Todd Macfarlan; James L. Manley; Debabrata Chakrav...
• Keywords: 0303 health sciences; Binding Sites; Serine-Arginine Splicing Factors; Mitosis; Nuclear Proteins; RNA-Binding Proteins; Cell Biology; Chromatin; Nucleosomes; Histones; 03 medical and health sciences; Serine; Animals; Humans; Phosphorylation; Molecular Biology; Chickens; Cells, Cultured; HeLa Cells

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 hyperphosphorylated 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 ASF/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.