| Title: |
Mapping and Analysis of Chromatin State Dynamics in Nine Human Cell Types |
| Authors: |
Ernst, Jason; Kheradpour, Pouya; Mikkelsen, Tarjei Sigurd; Shoresh, Noam; Ward, Lucas D.; Epstein, Charles B.; Zhang, Xiaolan; Wang, Li; Issner, Robbyn; Coyne, Michael J.; Ku, Manching; Durham, Timothy; Kellis, Manolis; Bernstein, Bradley E. |
| Contributors: |
Lincoln Laboratory; Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory; Massachusetts Institute of Technology. School of Science; Kellis, Manolis; Ernst, Jason; Kheradpour, Pouya; Ward, Lucas D.; Epstein, Charles B.; Coyne, Michael J.; Ku, Manching |
| Source: |
PubMed Central |
| Publisher Information: |
Nature Publishing Group |
| Publication Year: |
2010 |
| Collection: |
DSpace@MIT (Massachusetts Institute of Technology) |
| Description: |
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. ; National Human Genome Research Institute (U.S.) (R01HG004037) ; National Human Genome Research Institute (U.S.) (RC1HG005334) ; National Science Foundation (U.S.). (Award 0644282) ; National Science Foundation (U.S.). (Award 0905968) ; Alfred P. Sloan Foundation |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
http://dx.doi.org/10.1038/nature09906; Nature; https://hdl.handle.net/1721.1/72979; Ernst, Jason et al. “Mapping and Analysis of Chromatin State Dynamics in Nine Human Cell Types.” Nature 473.7345 (2011): 43–49. |
| Availability: |
https://hdl.handle.net/1721.1/72979 |
| Rights: |
Creative Commons Attribution-Noncommercial-Share Alike 3.0 ; http://creativecommons.org/licenses/by-nc-sa/3.0/ |
| Accession Number: |
edsbas.FE955217 |
| Database: |
BASE |