Publication Date:
2011-03-29
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3088773/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3088773/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ernst, Jason -- Kheradpour, Pouya -- Mikkelsen, Tarjei S -- Shoresh, Noam -- Ward, Lucas D -- Epstein, Charles B -- Zhang, Xiaolan -- Wang, Li -- Issner, Robbyn -- Coyne, Michael -- Ku, Manching -- Durham, Timothy -- Kellis, Manolis -- Bernstein, Bradley E -- R01 HG004037/HG/NHGRI NIH HHS/ -- R01HG004037/HG/NHGRI NIH HHS/ -- RC1HG005334/HG/NHGRI NIH HHS/ -- U54 HG004570/HG/NHGRI NIH HHS/ -- U54 HG004570-01/HG/NHGRI NIH HHS/ -- U54 HG004570-02/HG/NHGRI NIH HHS/ -- U54 HG004570-02S1/HG/NHGRI NIH HHS/ -- U54 HG004570-03/HG/NHGRI NIH HHS/ -- U54 HG004570-03S1/HG/NHGRI NIH HHS/ -- U54 HG004570-04/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 May 5;473(7345):43-9. doi: 10.1038/nature09906. Epub 2011 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21441907" target="_blank"〉PubMed〈/a〉
Keywords:
Binding Sites
;
Cell Line
;
Cell Line, Tumor
;
*Cell Physiological Phenomena
;
Cells, Cultured
;
Chromatin/*genetics/*metabolism
;
*Chromosome Mapping
;
Gene Expression Regulation
;
Genome, Human/genetics
;
Hep G2 Cells
;
Humans
;
Promoter Regions, Genetic/genetics
;
Reproducibility of Results
;
Transcription Factors/genetics
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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