Genomics

Dataset Information

35

Genomic Binding of Human Linker Histone H1.5 during differentiation (ChIP-chip)


ABSTRACT: 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. Overall design: ChIP-chip against H1.5 in human H1 ES cells, HSF1 ES cells, IMR90 cells, human keratinocytes, calcium induced keratinocytes, in vitro differentiated neural progenitor cells, in vitro differentiated neurons, primary human hepatocytes, H1.5 knockdown IMR90 cells, SIRT1 knockdown IMR90 cells. ChIP-chip against SIRT1 in IMR90 cells, H1.5 knockdown IMR90 cells. ChIP-chip against di-methyl histone H3 lysine 9 in IMR90 cells. ChIP-chip against RNA polymerase II in IMR90 cells.

INSTRUMENT(S): Agilent-014706 Human Promoter ChIP-on-Chip Set 244K, Microarray 1 of 2 G4489A (Feature Number version)

SUBMITTER: Jing-Yu Li  

PROVIDER: GSE26861 | GEO | 2012-09-18

SECONDARY ACCESSION(S): PRJNA142007

REPOSITORIES: GEO

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