Functional comparison of H1 histones in Xenopus reveals isoform-specific regulation by Cdk1 and RanGTP.
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.
Freedman
Benjamin S
BS
Molecular and Cell Biology Department, University of California, Berkeley, Berkeley, CA 94720-3200, USA.
Heald
Rebecca
R
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*
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
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