Isoform-specific phosphorylation of human linker histone H1.4 in mitosis by the kinase Aurora B.
Fiche publication
Date publication
mai 2011
Journal
Journal of cell science
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DAUJAT Sylvain
Tous les auteurs :
Hergeth SP, Dundr M, Tropberger P, Zee BM, Garcia BA, Daujat S, Schneider R
Lien Pubmed
Résumé
The linker histone H1 plays an essential role in maintaining and establishing higher-order chromatin structure. As with core histones, histone H1 is also extensively covalently modified. We showed previously that phosphorylation of S27 in human histone H1.4 (H1.4S27-P), prevents binding of heterochromatin protein 1 (HP1) family members (officially known as chromobox protein homologs) to the neighboring dimethylated K26. Here, we present the first functional characterization of H1.4S27-P in vivo and in vitro. We show that H1.4S27 phosphorylation is cell-cycle-regulated and its levels peak on metaphase chromosomes. We identify further Aurora B as the kinase phosphorylating H1.4S27. We demonstrate that histone H1.4 is the only somatic linker histone variant targeted by Aurora B and that Aurora B exclusively phosphorylates S27. Adjacent K26 dimethylation can regulate Aurora B activity towards S27, uncovering a crosstalk between these modifications. Finally, our fluorescence recovery after photobleaching (FRAP) analysis on histone H1.4 mutants suggests a role of S27 phosphorylation in the regulation of histone H1.4 mobility and chromatin binding in mitosis.
Mots clés
Animals, Aurora Kinase B, Aurora Kinases, Chromosomal Proteins, Non-Histone, chemistry, HeLa Cells, Heterochromatin, metabolism, Histones, chemistry, Humans, Methylation, Mice, Mitosis, physiology, NIH 3T3 Cells, Phosphorylation, Protein Isoforms, Protein-Serine-Threonine Kinases, metabolism, Substrate Specificity
Référence
J. Cell. Sci.. 2011 May;124(Pt 10):1623-8