1. Research Institute of Molecular Pathology, Dr. Bohrgasse 7, A-1030 Vienna, Austria
2. Department of Immunology, Monash University Medical School, Commercial Road, Prahran, Victoria 3181, Australia
3. Present address: Department of Experimental Pathology, Cancer Institute, Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo 135-8550, Japan

Correspondence to: Jan-Michael Peters¹ Correspondence and requests for materials should be addressed to J.-M.P. (Email: peters@imp.univie.ac.at).

Abstract

Histones are subject to numerous post-translational modifications¹. 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 ⁷. 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 chromatin⁸, but any such mechanisms are unknown. Here we show that antibodies against mitotic chromosomal antigens that are associated with human autoimmune diseases⁹ 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^{10, 11, 12}, 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' mechanism⁸ that displaces HP1 and perhaps other proteins from mitotic heterochromatin.

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