Histone H3 serine 10 phosphorylation by Aurora B causes HP1 dissociation from heterochromatin

Abstract

Histones are subject to numerous post-translational modifications. Some of these 'epigenetic' marks recruit proteins that modulate chromatin structure. For example, heterochromatin protein 1 (HP1) binds to histone H3 when its lysine 9 residue has been tri-methylated by the methyltransferase Suv39h (refs 2-6). During mitosis, H3 is also phosphorylated by the kinase Aurora B. Although H3 phosphorylation is a hallmark of mitosis, its function remains mysterious. It has been proposed that histone phosphorylation controls the binding of proteins to chromatin, but any such mechanisms are unknown. Here we show that antibodies against mitotic chromosomal antigens that are associated with human autoimmune diseases specifically recognize H3 molecules that are modified by both tri-methylation of lysine 9 and phosphorylation of serine 10 (H3K9me3S10ph). The generation of H3K9me3S10ph depends on Suv39h and Aurora B, and occurs at pericentric heterochromatin during mitosis in different eukaryotes. Most HP1 typically dissociates from chromosomes during mitosis, but if phosphorylation of H3 serine 10 is inhibited, HP1 remains chromosome-bound throughout mitosis. H3 phosphorylation by Aurora B is therefore part of a 'methyl/phos switch' mechanism that displaces HP1 and perhaps other proteins from mitotic heterochromatin.

HDAC3: taking the SMRT-N-CoRrect road to repression

“…HDAC3-mediated deacetylation of histones during mitosis is required for subsequent phosphorylation of H3 on Ser10 by the aurora kinase B (Li et al, 2006). H3 Ser10 phosphorylation is, in turn, required for HP1 dissociation, proper chromosome condensation and segregation (Wei et al, 1999;Fischle et al, 2005;Hirota et al, 2005). This example illustrates a nontranscriptional effect of HDAC3 during mitosis.…”

Shugoshin regulates cohesion by driving relocalization of PP2A in Xenopus extracts

“…In the case of Aurora B, Sgo appears not to be the only relevant target of the kinase in this prophase pathway. Other possible targets could be condensin, heterochromatin protein 1 (HP1), or some other protein yet to be identified (Fischle et al 2005;Hirota et al 2005;Lipp et al 2007). …”

The essential role of acetyllysine binding by the YEATS domain in transcriptional regulation

“…27 As H3K9me3 recruitment is negatively regulated, in part, through phosphorylation of neighboring serine 10 (H3S10ph), this finding has given rise to the concept of a 'phospho-methyl' switch. 28,29 A similar switch has been shown to eject the H3K4me3-interacting PHD fingers when neighboring H3T3 or H3T6 are phosphorylated. [30][31][32][33] To assess whether 'phospho-acetyl' switches can regulate the function of Taf14, we evaluated binding activity of the Taf14 YEATS domain toward histone peptides harboring S10ph and T6ph modifications along with H3K9ac ( Fig.…”