DNA methylation promotes Aurora-B-driven phosphorylation of histone H3 in chromosomal subdomainsReportar como inadecuado

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1 BMC - Laboratoire de biologie moléculaire de la cellule 2 The Scripps Research Institute San Diego

Abstract : 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 immuno-fluorescent 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.

Keywords : Pericentromeres heterochromatin Aurora-B Histone H3 phosphorylation DNA methylation G2 phase

Autor: Karine Monier - Sandrine Mouradian - Kevin Sullivan -

Fuente: https://hal.archives-ouvertes.fr/


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