@article {613, title = {Histone modifications at human enhancers reflect global cell-type-specific gene expression.}, journal = {Nature}, volume = {459}, year = {2009}, month = {2009 May 7}, pages = {108-12}, 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.}, keywords = {Binding Sites, Cell Line, Cell Physiological Phenomena, Chromatin, Gene Expression Regulation, Genome, Human, HeLa Cells, Histones, Humans, K562 Cells, Promoter Regions, Genetic, Transcription Factors}, issn = {1476-4687}, doi = {10.1038/nature07829}, author = {Heintzman, Nathaniel D and Hon, Gary C and Hawkins, R David and Kheradpour, Pouya and Stark, Alexander and Harp, Lindsey F and Ye, Zhen and Lee, Leonard K and Stuart, Rhona K and Ching, Christina W and Ching, Keith A and Antosiewicz-Bourget, Jessica E and Liu, Hui and Zhang, Xinmin and Green, Roland D and Lobanenkov, Victor V and Stewart, Ron and Thomson, James A and Crawford, Gregory E and Kellis, Manolis and Ren, Bing} }