title: Functional comparison of H1 histones in Xenopus reveals isoform-specific regulation by Cdk1 and RanGTP.
abstract: H1 "linker" histones bind dynamically to nucleosomes and promote their compaction into chromatin fibers. Developmental H1 isoforms are evolutionarily conserved, but their function, regulation, and posttranslational modifications are poorly understood. In Xenopus egg extracts, the embryonic linker histone H1M does not affect nuclear assembly or replication but is required for proper chromosome architecture during mitosis. We report here that somatic H1 isoforms, which are more positively charged and feature multiple Cdk1 phosphorylation sites, cannot substitute for H1M at endogenous concentrations, instead causing chromatin compaction during interphase and dissociating from chromosomes at the onset of mitosis. Mitotic Cdk1 phosphorylation is not responsible for this dissociation and instead functions to enhance H1 binding in egg extracts and embryos. Nuclear import receptors RanBP7 and importin beta bind tightly to somatic H1 but not H1M, and addition of a constitutively active Ran mutant abolishes this interaction and enhances the ability of somatic H1 to rescue mitotic chromosome architecture. Our results reveal distinct regulatory mechanisms among linker histone isoforms and a specific role for H1M to compact chromosomes during egg meiotic arrest and early embryonic divisions.
authors.affiliation: Molecular and Cell Biology Department, University of California, Berkeley, Berkeley, CA 94720-3200, USA.
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Freedman
authors.forename: Rebecca
authors.initials: R
authors.lastname: Heald
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D002875:Chromosomes / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007399:Interphase; D028884:Karyopherins / Q000378:metabolism; D008938:Mitosis; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D029867:Xenopus Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D006657:Histones; D028884:Karyopherins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D029867:Xenopus Proteins; D016203:CDC2 Protein Kinase; D020931:ran GTP-Binding Protein
references.citation: Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12477-81
references.pmid: 7809061
references.citation: J Cell Biol. 2005 Jun 20;169(6):859-69
references.pmid: 15967810
references.citation: Dev Biol. 1993 Nov;160(1):214-27
references.pmid: 8224538
references.citation: EMBO J. 1999 May 4;18(9):2411-23
references.pmid: 10228156
references.citation: EMBO J. 1989 Oct;8(10):3059-69
references.pmid: 2573514
references.citation: Science. 2002 Mar 29;295(5564):2452-6
references.pmid: 11923538
references.citation: Nature. 2006 Mar 30;440(7084):697-701
references.pmid: 16572176
references.citation: Methods Cell Biol. 1991;36:581-605
references.pmid: 1839804
references.citation: Nature. 2000 Dec 14;408(6814):873-6
references.pmid: 11130728
references.citation: Dev Biol. 1994 Feb;161(2):425-39
references.pmid: 8313993
references.citation: Cell. 1977 Sep;12(1):101-7
references.pmid: 561660
references.citation: Anal Biochem. 1991 Feb 1;192(2):262-7
references.pmid: 1852137
references.citation: Gene. 2009 Feb 15;431(1-2):1-12
references.pmid: 19059319
references.citation: Proc Natl Acad Sci U S A. 1976 Jun;73(6):1897-901
references.pmid: 1064861
references.citation: Methods Mol Biol. 2006;322:459-74
references.pmid: 16739744
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5697-702
references.pmid: 15821029
references.citation: J Biochem. 2008 Mar;143(3):287-93
references.pmid: 18234717
references.citation: EMBO J. 2002 Feb 1;21(3):377-86
references.pmid: 11823430
references.citation: Cell Biochem Funct. 2006 Mar-Apr;24(2):93-4
references.pmid: 16245369
references.citation: Biol Chem. 2008 Apr;389(4):333-43
references.pmid: 18208346
references.citation: Nature. 2000 Dec 14;408(6814):877-81
references.pmid: 11130729
references.citation: Cell. 2001 Jan 12;104(1):95-106
references.pmid: 11163243