Genomics

Dataset Information

30

Global Chromatin Modifications at Enhancers Correlate with Cell Type-Specific Gene Expression in the Human Genome


ABSTRACT: The human body is composed of diverse cell types with distinct functions. While it is known that lineage specification depends on cell specific gene expression, which in turn is driven by promoters, enhancers, insulators and other cis-regulatory DNA sequences for each gene1-3, the relative roles of these regulatory elements in this process is not clear. We have previously developed a chromatin immunoprecipitation-based microarray method (ChIP-chip) to identify promoters, enhancers and insulator elements in the human genome4-6. Here, we use the same approach to identify these active elements in multiple cell types and investigated their roles in cell type-specific gene expression. We observed that chromatin state at promoters and CTCF-binding at insulators are largely invariant across diverse cell types. By contrast, enhancers are marked with highly cell type-specific histone modification patterns, strongly correlate to cell type-specific gene expression programs on a global scale, and are functionally active in a cell type-specific manner. Our results defined over 55, 000 potential transcriptional enhancers in the human genome, significantly expanding the current catalog of human enhancers and highlighting the role of these elements in cell type-specific gene expression. Keywords: ChIP-chip Overall design: In HeLa cells, we mapped histone modifications H3K4me1 and H3K4me3, as well as binding of the transcription factor STAT1, genome-wide using ChIP-chip. We predicted almost 40,000 transcriptional enhancers using chromatin signatures, designed condensed microarrays to span these enhancers, and then verified them by examining the following marks in replicate experiments: H3K4me1, H3K4me3, H3K27ac, p300, and MED1. We also performed DNase-chip to map regions of DNase I hypersensitivity. Finally, we repeated these experiments in K562 cells, mapping H3K4me1, H3K4me3, H3K27ac, and STAT1 binding genome-wide using ChIP-chip.

REANALYSED by: GSE119128

INSTRUMENT(S): [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array

SUBMITTER: Gary Chung Hon 

PROVIDER: GSE14083 | GEO | 2009-03-01

SECONDARY ACCESSION(S): PRJNA112507

REPOSITORIES: GEO

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Publications


The human body is composed of diverse cell types with distinct functions. Although it is known that lineage specification depends on cell-specific gene expression, which in turn is driven by promoters, enhancers, insulators and other cis-regulatory DNA sequences for each gene, the relative roles of these regulatory elements in this process are not clear. We have previously developed a chromatin-immunoprecipitation-based microarray method (ChIP-chip) to locate promoters, enhancers and insulators  ...[more]

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