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First published online 12 December 2006
doi: 10.1242/jcs.03326

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DNA methylation promotes Aurora-B-driven phosphorylation of histone H3 in chromosomal subdomains

Karine Monier^1,2,*, Sandrine Mouradian² and Kevin F. Sullivan^1,

¹ The Scripps Research Institute, Department of Cell Biology, CB163, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA
² Group Epigenetics of Pericentromeres, Laboratory of Molecular Biology of the Cell, CNRS UMR 5161, INRA U 1237, IFR 128, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon CEDEX 07, France

^* Author for correspondence (e-mail: kmonier{at}ens-lyon.fr)

Accepted 23 October 2006

Confinement of enzymatic reactions to nuclear and chromosomal subdomains regulates functional organization of the nucleus. Aurora-B kinase regulates cell-cycle-dependent phosphorylation of chromosomal substrates through sequential localization to a series of sites on chromosomes and the mitotic spindle. In G2 nuclei, Aurora-B recruitment to heterochromatin restricts histone H3S10 phosphorylation to a domain around centromeres (pericentromeres). However, no intrinsic chromosomal determinants have been implicated in Aurora-B recruitment to interphase pericentromeres. Using cyclin B1 as a cell-cycle marker, we found that the great majority of nuclei exhibiting H3S10 phosphorylated foci were positive for cyclin B1, thus revealing that H3S10 phosphorylation arises at pericentromeres during late S phase and persists in G2. By immunofluorescent in situ hybridization, Aurora-B and H3S10 phosphorylated foci were found more frequently at larger pericentromeres than at smaller ones, revealing a preferential phosphorylation of pericentromeres, exhibiting a high density of methyl cytosines. Disruption of DNA methylation inhibited pericentromeric Aurora-B targeting and H3S10 phosphorylation in G2 nuclei, thus demonstrating the role of DNA methylation in Aurora-B targeting to pericentromeres. These results favour the idea that DNA methylation maintains a local environment essential for regulating the functional properties of sub-chromosomal domains during S-G2 progression.

Key words: Pericentromeres, Heterochromatin, Aurora-B, Histone H3 phosphorylation, DNA methylation, G2 phase

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