title: Linker histone H1.2 establishes chromatin compaction and gene silencing through recognition of H3K27me3.
abstract: Linker histone H1 is a protein component of chromatin and has been linked to higher-order chromatin compaction and global gene silencing. However, a growing body of evidence suggests that H1 plays a gene-specific role, regulating a relatively small number of genes. Here we show that H1.2, one of the H1 subtypes, is overexpressed in cancer cells and contributes to gene silencing. H1.2 gets recruited to distinct chromatin regions in a manner dependent on EZH2-mediated H3K27me3, and inhibits transcription of multiple growth suppressive genes via modulation of chromatin architecture. The C-terminal tail of H1.2 is critical for the observed effects, because mutations of three H1.2-specific amino acids in this domain abrogate the ability of H1.2 to bind H3K27me3 nucleosomes and inactivate target genes. Collectively, these results provide a molecular explanation for H1.2 functions in the regulation of chromatin folding and indicate that H3K27me3 is a key mechanism governing the recruitment and activity of H1.2 at target loci.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA.|Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Jin-Man
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA.|Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.|Department of Biology, College of Natural Sciences, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Kyunghwan
authors.initials: K
authors.lastname: Kim
authors.affiliation: Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.|Department of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Vasu
authors.initials: V
authors.lastname: Punj
authors.affiliation: Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Gangning
authors.initials: G
authors.lastname: Liang
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA.|Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Tobias S
authors.initials: TS
authors.lastname: Ulmer
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA.|Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Wange
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA.|Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Woojin
authors.initials: W
authors.lastname: An
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002843:Chromatin / Q000378:metabolism*; D000071221:Enhancer of Zeste Homolog 2 Protein; D020868:Gene Silencing; D056426:Genetic Loci; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D009707:Nucleosomes / Q000378:metabolism; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism; D011485:Protein Binding; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D008239:Lysine