Human Linker Histone H1.5
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Jing-Yu Li
PROVIDER: E-GEOD-26979 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Linker histones are essential components of chromatin but the distributions and functions of many during cellular differentiation is not well understood. Here, we show that H1.5 binds to genic and intergenic regions, forming blocks of enrichment, in differentiated human cells from all three embryonic germ layers but not in embryonic stem cells. In differentiated cells, H1.5, but not H1.3, binds preferentially to genes that encode membrane and membrane-related proteins. Strikingly, 37% of H1.5 target genes belong to gene family clusters, groups of homologous genes that are located in proximity to each other on chromosomes. H1.5 binding is associated with gene repression and is required for SIRT1 binding, H3K9me2 enrichment and chromatin compaction. Depletion of H1.5 results in loss of SIRT1 and H3K9me2, increased chromatin accessibility, deregulation of gene expression and decreased cell growth. Our data reveal for the first time a specific and novel function for linker histone subtype H1.5 in maintenance of condensed chromatin at defined gene families in differentiated human cells. Examine human linker histone H1.5 (HIST1H1B) binding pattern in H1 hESCs and IMR90 fibroblasts
2012-12-11 | E-GEOD-26967 | biostudies-arrayexpress
Project description:In humans, there are eleven subtypes of linker histones that exhibit cell- and tissue-specific expression. Linker histone H1 proteins bind to both the core histones and linker DNA of chromatin fibers; and not only participate in control of gene activity but also serve to stabilize higher order chromatin structure. To determine the potential roles of linker histones in differentiation, we examined the global distribution of linker histone subtype H1.5 in human IMR90 fibroblasts and H1 embryonic stem cells (hESCs). Surprisingly, H1.5 binds to and represses a large fraction of gene family clusters in fully differentiated cell types representing all three embryonic germ layers. Little or no H1.5 enrichment at gene family clusters was detected in undifferentiated hESCs or partially differentiated somatic cells. We also found that SIRT1 histone deacetylase and H3K9me2, a repressive histone modification, are also enriched at gene family cluster in IMR90 cells, likely generating a stably repressive chromatin domain. To find out the mechanism of H1.5 targeting, H1.5 or SIRT1 was depleted in IMR90 cells by siRNA, and the binding patterns of SIRT1 and H1.5 were examined. In H1.5 knockdown cells, SIRT1 binding pattern was changed dramatically, and this changed pattern highly correlates to SIRT1 distribution in hESC. However, depletion of SIRT1 could not change the global binding pattern of H1.5. Depletion of H1.5 or SIRT1 leads to up-regulation of ~50% gene family clusters. However, the sets of gene family clusters that are affected by these two factors are different, suggesting H1.5 and SIRT1 may regulate gene transcription via different pathways. Two-color microarrays. Two replicates for each sample.
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Project description:In humans, there are eleven subtypes of linker histones that exhibit cell- and tissue-specific expression. Linker histone H1 proteins bind to both the core histones and linker DNA of chromatin fibers; and not only participate in control of gene activity but also serve to stabilize higher order chromatin structure. To determine the potential roles of linker histones in differentiation, we examined the global distribution of linker histone subtype H1.5 in human IMR90 fibroblasts and H1 embryonic stem cells (hESCs). Surprisingly, H1.5 binds to and represses a large fraction of gene family clusters in fully differentiated cell types representing all three embryonic germ layers. Little or no H1.5 enrichment at gene family clusters was detected in undifferentiated hESCs or partially differentiated somatic cells. We also found that SIRT1 histone deacetylase and H3K9me2, a repressive histone modification, are also enriched at gene family cluster in IMR90 cells, likely generating a stably repressive chromatin domain. To find out the mechanism of H1.5 targeting, H1.5 or SIRT1 was depleted in IMR90 cells by siRNA, and the binding patterns of SIRT1 and H1.5 were examined. In H1.5 knockdown cells, SIRT1 binding pattern was changed dramatically, and this changed pattern highly correlates to SIRT1 distribution in hESC. However, depletion of SIRT1 could not change the global binding pattern of H1.5. Depletion of H1.5 or SIRT1 leads to up-regulation of ~50% gene family clusters. However, the sets of gene family clusters that are affected by these two factors are different, suggesting H1.5 and SIRT1 may regulate gene transcription via different pathways. One-color array. Two replicates for each sample.
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Project description:Linker histones are essential components of chromatin but the distributions and functions of many during cellular differentiation is not well understood. Here, we show that H1.5 binds to genic and intergenic regions, forming blocks of enrichment, in differentiated human cells from all three embryonic germ layers but not in embryonic stem cells. In differentiated cells, H1.5, but not H1.3, binds preferentially to genes that encode membrane and membrane-related proteins. Strikingly, 37% of H1.5 target genes belong to gene family clusters, groups of homologous genes that are located in proximity to each other on chromosomes. H1.5 binding is associated with gene repression and is required for SIRT1 binding, H3K9me2 enrichment and chromatin compaction. Depletion of H1.5 results in loss of SIRT1 and H3K9me2, increased chromatin accessibility, deregulation of gene expression and decreased cell growth. Our data reveal for the first time a specific and novel function for linker histone subtype H1.5 in maintenance of condensed chromatin at defined gene families in differentiated human cells. Examine mRNA expression in control and H1.5 knockdown IMR90 cells
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Project description:Although the function of DNA methylation in gene promoter regions is well established in transcriptional repression, the function of the evolutionarily conserved widespread distribution of DNA methylation in gene body regions remains incompletely understood. Here, we show that DNA methylation is enriched in included alternatively spliced exons (ASEs) and inhibiting DNA methylation results in aberrant splicing of ASEs. The methyl-CpG binding protein MeCP2 is enriched in included ASEs, particularly those that are also highly DNA methylated, and inhibition of DNA methylation disrupts specific targeting of MeCP2 to exons. Interestingly, ablation of MeCP2 results in increased nucleosome acetylation and aberrant skipping events of ASEs. We further show that inhibition of histone deacetylases leads to a highly significant overlap of exon skipping events caused by knocking-down MeCP2. Together, our data indicate that intragenic DNA methylation operates in exon definition to modulate alternative splicing and can enhance exon recognition via recruitment of the multifunctional protein MeCP2, which thereby maintains local histone hypoacetylation through its established interaction with HDACs. RNA-Seq in IMR90 and HCT116
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