Functional Comparison of H1 Histones in Xenopus Reveals Isoform-Specific Regulation by Cdk1 and RanGTP

SummaryH1 “linker” histones bind dynamically to nucleosomes and promote their compaction into chromatin fibers [1, 2, 3 and 4]. Developmental H1 isoforms are evolutionarily conserved, but their function, regulation, and posttranslational modifications are poorly understood [5, 6 and 7]. 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 [ 8 and 9]. 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 β 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.

Graphical AbstractFigure optionsDownload high-quality image (327 K)Download as PowerPoint slideHighlights
► Somatic H1 compacts interphase chromatin but, unlike H1M, dissociates at mitosis
► Cdk1 phosphorylation of somatic H1 enhances its binding to mitotic chromosomes
► RanGTP releases somatic H1 from importin β/RanBP7 to promote chromatin binding