title: Genome distribution of replication-independent histone H1 variants shows H1.0 associated with nucleolar domains and H1X associated with RNA polymerase II-enriched regions.
abstract: Unlike core histones, the linker histone H1 family is more evolutionarily diverse, and many organisms have multiple H1 variants or subtypes. In mammals, the H1 family includes seven somatic H1 variants; H1.1 to H1.5 are expressed in a replication-dependent manner, whereas H1.0 and H1X are replication-independent. Using ChIP-sequencing data and cell fractionation, we have compared the genomic distribution of H1.0 and H1X in human breast cancer cells, in which we previously observed differential distribution of H1.2 compared with the other subtypes. We have found H1.0 to be enriched at nucleolus-associated DNA repeats and chromatin domains, whereas H1X is associated with coding regions, RNA polymerase II-enriched regions, and hypomethylated CpG islands. Further, H1X accumulates within constitutive or included exons and retained introns and toward the 3' end of expressed genes. Inducible H1X knockdown does not affect cell proliferation but dysregulates a subset of genes related to cell movement and transport. In H1X-depleted cells, the promoters of up-regulated genes are not occupied specifically by this variant, have a lower than average H1 content, and, unexpectedly, do not form an H1 valley upon induction. We conclude that H1 variants are not distributed evenly across the genome and may participate with some specificity in chromatin domain organization or gene regulation.
authors: From the Institut de Biologia Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona, Catalonia 08028 Spain.
authors: Regina
authors: R
authors: Mayor
authors: From the Institut de Biologia Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona, Catalonia 08028 Spain.
authors: Andrea
authors: A
authors: Izquierdo-Bouldstridge
authors: From the Institut de Biologia Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona, Catalonia 08028 Spain.
authors: Lluís
authors: L
authors: Millán-Ariño
authors: From the Institut de Biologia Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona, Catalonia 08028 Spain.
authors: Alberto
authors: A
authors: Bustillos
authors: From the Institut de Biologia Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona, Catalonia 08028 Spain.
authors: Cristina
authors: C
authors: Sampaio
authors: From the Institut de Biologia Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona, Catalonia 08028 Spain.
authors: Neus
authors: N
authors: Luque
authors: From the Institut de Biologia Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona, Catalonia 08028 Spain albert.jordan@ibmb.csic.es.
authors: Albert
authors: A
authors: Jordan
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000235:genetics*; D049109:Cell Proliferation; D018899:CpG Islands; D004247:DNA / Q000235:genetics; D017931:DNA Primers; D005091:Exons; D015894:Genome, Human; D006657:Histones / Q000235:genetics*; D006801:Humans; D016133:Polymerase Chain Reaction; D012319:RNA Polymerase II / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D006657:Histones; D004247:DNA; D012319:RNA Polymerase II
keywords: Chromatin; Epigenetics; H1.0; H1X; Histone; Histone H1; Nucleolus; RNA Polymerase II; Variants
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