Dai, J., Sultan, S., Taylor, S.S. & Higgins, J.M. The kinase haspin is required for mitotic histone H3 Thr 3 phosphorylation and normal metaphase chromosome alignment. Genes Dev. 19, 472-488

Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Genes & Development (Impact Factor: 10.8). 03/2005; 19(4):472-88. DOI: 10.1101/gad.1267105
Source: PubMed


Post-translational modifications of conserved N-terminal tail residues in histones regulate many aspects of chromosome activity. Thr 3 of histone H3 is highly conserved, but the significance of its phosphorylation is unclear, and the identity of the corresponding kinase unknown. Immunostaining with phospho-specific antibodies in mammalian cells reveals mitotic phosphorylation of H3 Thr 3 in prophase and its dephosphorylation during anaphase. Furthermore we find that haspin, a member of a distinctive group of protein kinases present in diverse eukaryotes, phosphorylates H3 at Thr 3 in vitro. Importantly, depletion of haspin by RNA interference reveals that this kinase is required for H3 Thr 3 phosphorylation in mitotic cells. In addition to its chromosomal association, haspin is found at the centrosomes and spindle during mitosis. Haspin RNA interference causes misalignment of metaphase chromosomes, and overexpression delays progression through early mitosis. This work reveals a new kinase involved in composing the histone code and adds haspin to the select group of kinases that integrate regulation of chromosome and spindle function during mitosis and meiosis.

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    • "Furthermore, the signal from H3T3P immunostaining (Figure S1E) was enriched, but not restricted, to the centromeric region labeled with an antibody against a centromere-specific H3 variant centromere identifier (Cid) (Figure S1E). In summary, the temporal and spatial distributions of H3T3P in Drosophila male germ cells are comparable to what has been reported in other cell types from other systems (Caperta et al., 2008; Dai et al., 2005; Escribá and Goday, 2013; Markaki et al., 2009; Wang et al., 2010). "
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    • "The kinase that generates the H3T3P mark has been identified to be the Haspin protein (Dai et al., 2005). By driving a short hairpin RNA (shRNA) (Ni et al., 2011) with the nos-Gal4 driver to knock down haspin, specifically in early-stage germ cells, we were able to observe a significant decrease of H3T3P in GSCs (Figure S7A). "
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    ABSTRACT: Graphical Abstract Highlights d Pre-existing versus newly synthesized H3 are separable in prophase germline stem cell d H3 threonine 3 phosphorylation distinguishes pre-existing from newly synthesized H3 d Both H3T3A and H3T3D mutations randomize H3 inheritance patterns In Brief A transient mitosis-specific phosphate modification on histone H3 distinguishes pre-existing and newly synthesized histones and is required for the asymmetric segregation of sister chromatids—one enriched with new histones and the other with old—during stem cell division.
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    • "Thus, in addition to H3K4me3, the phosphorylation of T3 and T6, but not S10, probably acts as additional ''on/off switches'' (Fischle et al., 2003) to control the sites at which Dnmt3a associates with chromatin. H3T3ph appears exclusively during mitosis (Dai et al., 2005; Markaki et al., 2009) and H3T6ph occurs mainly during interphase (Garske et al., 2010; Metzger et al., 2010). "
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