Article

Histone Modifications at Human Enhancers Reflect Global Cell-Type-Specific Gene Expression

Ludwig Institute for Cancer Research, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, California 92093-0653, USA.
Nature (Impact Factor: 41.46). 04/2009; 459(7243):108-12. DOI: 10.1038/nature07829
Source: PubMed

ABSTRACT

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 in the human genome. Here we use the same approach to identify these elements in multiple cell types and investigate their roles in cell-type-specific gene expression. We observed that the chromatin state at promoters and CTCF-binding at insulators is largely invariant across diverse cell types. In 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 define over 55,000 potential transcriptional enhancers in the human genome, significantly expanding the current catalogue of human enhancers and highlighting the role of these elements in cell-type-specific gene expression.

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    • "However, the mechanisms that restrict enhancer activity to a single promoter in the presence of multiple promoter choices are unclear. Enhancers carry a unique chromatin structure characterized by the presence of 3K4me1 (Heintzman et al. 2009). In addition, histone H3K27ac distinguishes active enhancers from poised enhancers (Creyghton et al. 2010). "
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