title: Mapping and analysis of chromatin state dynamics in nine human cell types.
abstract: Chromatin profiling has emerged as a powerful means of genome annotation and detection of regulatory activity. The approach is especially well suited to the characterization of non-coding portions of the genome, which critically contribute to cellular phenotypes yet remain largely uncharted. Here we map nine chromatin marks across nine cell types to systematically characterize regulatory elements, their cell-type specificities and their functional interactions. Focusing on cell-type-specific patterns of promoters and enhancers, we define multicell activity profiles for chromatin state, gene expression, regulatory motif enrichment and regulator expression. We use correlations between these profiles to link enhancers to putative target genes, and predict the cell-type-specific activators and repressors that modulate them. The resulting annotations and regulatory predictions have implications for the interpretation of genome-wide association studies. Top-scoring disease single nucleotide polymorphisms are frequently positioned within enhancer elements specifically active in relevant cell types, and in some cases affect a motif instance for a predicted regulator, thus suggesting a mechanism for the association. Our study presents a general framework for deciphering cis-regulatory connections and their roles in disease.
authors: Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
authors: Jason
authors: J
authors: Ernst
authors: Pouya
authors: P
authors: Kheradpour
authors: Tarjei S
authors: TS
authors: Mikkelsen
authors: Noam
authors: N
authors: Shoresh
authors: Lucas D
authors: LD
authors: Ward
authors: Charles B
authors: CB
authors: Epstein
authors: Xiaolan
authors: X
authors: Zhang
authors: Li
authors: L
authors: Wang
authors: Robbyn
authors: R
authors: Issner
authors: Michael
authors: M
authors: Coyne
authors: Manching
authors: M
authors: Ku
authors: Timothy
authors: T
authors: Durham
authors: Manolis
authors: M
authors: Kellis
authors: Bradley E
authors: BE
authors: Bernstein
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D045744:Cell Line, Tumor; D002468:Cell Physiological Phenomena; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism*; D002874:Chromosome Mapping; D005786:Gene Expression Regulation; D015894:Genome, Human / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D015203:Reproducibility of Results; D014157:Transcription Factors / Q000235:genetics
chemical_list: D002843:Chromatin; D014157:Transcription Factors