Journal Article

Mapping and analysis of chromatin state dynamics in nine human cell types

Kheradpour, Pouya, Zhang, Xiaolan, Wang, Li, Coyne, Michael, Issner, Robbyn, Durham, Timothy, Ku, Manching, Epstein, Charles B., Shoresh, Noam, Kellis, Manolis, Bernstein, Bradley E., Mikkelsen, Tarjei S., Ernst, Jason, Ward, Lucas D.

2011

Overview

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. Genome annotation using chromatin profiles Large-scale chromatin profiling can be used to distinguish functional genomic elements. Here, a compendium of chromatin maps for various histone marks in multiple human cell types is presented. Using the resulting data it is possible to identify different chromatin states corresponding to distinct regulatory elements such as repressed and active promoters, enhancers and insulators. Several disease-associated single nucleotide polymorphisms are shown to overlap with regulatory elements. This work has implications for human disease, and in particular for interpreting genome-wide association studies.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/1647/1513/1382 / 631/337/100 / 692/420/2489/144 / Binding Sites / Biological and medical sciences / Cell Line / Cell Line, Tumor / Cell Physiological Phenomena / Cells, Cultured / Cellular biology / Chromatin / Chromatin - genetics / Chromatin - metabolism / Chromatin. Chromosome / Chromosome Mapping / Disease / Fundamental and applied biological sciences. Psychology / Gene expression / Gene Expression Regulation / Genome, Human - genetics / Genomes / Hep G2 Cells / Humanities and Social Sciences / Humans / Mechanical properties / Molecular and cellular biology / Molecular genetics / multidisciplinary / Promoter Regions, Genetic - genetics / Proteins / Reproducibility of Results / RNA polymerase / Science / Science (multidisciplinary) / Stem cells / Transcription Factors - genetics