title: Isoform-specific phosphorylation of human linker histone H1.4 in mitosis by the kinase Aurora B.
abstract: 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.
authors.affiliation: Max-Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany.
authors.forename: Sonja P
authors.initials: SP
authors.lastname: Hergeth
authors.forename: Miroslav
authors.initials: M
authors.lastname: Dundr
authors.forename: Philipp
authors.initials: P
authors.lastname: Tropberger
authors.forename: Barry M
authors.initials: BM
authors.lastname: Zee
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Garcia
authors.forename: Sylvain
authors.initials: S
authors.lastname: Daujat
authors.forename: Robert
authors.initials: R
authors.lastname: Schneider
mesh_terms: D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006570:Heterochromatin / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D051379:Mice; D008938:Mitosis / Q000502:physiology; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D006657:Histones; D020033:Protein Isoforms; D000090266:Chromobox Protein Homolog 5; C576921:AURKB protein, human; C576924:Aurkb protein, mouse; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases