title: Distinct properties of human HMGN5 reveal a rapidly evolving but functionally conserved nucleosome binding protein.
abstract: The HMGN family is a family of nucleosome-binding architectural proteins that affect the structure and function of chromatin in vertebrates. We report that the HMGN5 variant, encoded by a gene located on chromosome X, is a rapidly evolving protein with an acidic C-terminal domain that differs among vertebrate species. We found that the intranuclear organization and nucleosome interactions of human HMGN5 are distinct from those of mouse HMGN5 and that the C-terminal region of the protein is the main determinant of the chromatin interaction properties. Despite their apparent differences, both mouse and human HMGN5 proteins interact with histone H1, reduce its chromatin residence time, and can induce large-scale chromatin decompaction in living cells. Analysis of HMGN5 mutants suggests that distinct domains in HMGN5 affect specific steps in the interaction of H1 with chromatin. Elevated levels of either human or mouse HMGN5 affect the transcription of numerous genes, most in a variant-specific manner. Our study identifies HMGN5 as a rapidly evolving vertebrate nuclear protein with species-specific properties. HMGN5 has a highly disordered structure, binds dynamically to nucleosome core particles, modulates the binding of H1 to chromatin, reduces the compaction of the chromatin fiber, and affects transcription.
authors.affiliation: Protein Section, Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Cedric
authors.initials: C
authors.lastname: Malicet
authors.forename: Mark
authors.initials: M
authors.lastname: Rochman
authors.forename: Yuri
authors.initials: Y
authors.lastname: Postnikov
authors.forename: Michael
authors.initials: M
authors.lastname: Bustin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D041321:Chromosomes, Human, X / Q000235:genetics; D017124:Conserved Sequence; D015870:Gene Expression; D020869:Gene Expression Profiling; D024001:HMGN Proteins / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D024001:HMGN Proteins; C429289:HMGN5 protein, human; D006657:Histones; D034741:RNA, Small Interfering; D015534:Trans-Activators