Publication Date:
2013-10-19
Description:
The majority of disease-associated variants lie outside protein-coding regions, suggesting a link between variation in regulatory regions and disease predisposition. We studied differences in chromatin states using five histone modifications, cohesin, and CTCF in lymphoblastoid lines from 19 individuals of diverse ancestry. We found extensive signal variation in regulatory regions, which often switch between active and repressed states across individuals. Enhancer activity is particularly diverse among individuals, whereas gene expression remains relatively stable. Chromatin variability shows genetic inheritance in trios, correlates with genetic variation and population divergence, and is associated with disruptions of transcription factor binding motifs. Overall, our results provide insights into chromatin variation among humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075767/" 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/PMC4075767/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kasowski, Maya -- Kyriazopoulou-Panagiotopoulou, Sofia -- Grubert, Fabian -- Zaugg, Judith B -- Kundaje, Anshul -- Liu, Yuling -- Boyle, Alan P -- Zhang, Qiangfeng Cliff -- Zakharia, Fouad -- Spacek, Damek V -- Li, Jingjing -- Xie, Dan -- Olarerin-George, Anthony -- Steinmetz, Lars M -- Hogenesch, John B -- Kellis, Manolis -- Batzoglou, Serafim -- Snyder, Michael -- R01 HG004037/HG/NHGRI NIH HHS/ -- T32 GM007205/GM/NIGMS NIH HHS/ -- T32 HG000044/HG/NHGRI NIH HHS/ -- T32GM07205/GM/NIGMS NIH HHS/ -- U01 HL107393/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2013 Nov 8;342(6159):750-2. doi: 10.1126/science.1242510. Epub 2013 Oct 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24136358" target="_blank"〉PubMed〈/a〉
Keywords:
Binding Sites
;
Cell Cycle Proteins/genetics/metabolism
;
Cell Line, Tumor
;
Chromatin/*genetics/*metabolism
;
Chromosomal Proteins, Non-Histone/genetics/metabolism
;
Enhancer Elements, Genetic/genetics
;
*Gene Expression Regulation
;
Genetic Predisposition to Disease/*genetics
;
Genetic Variation
;
Histones/genetics/metabolism
;
Humans
;
Repressor Proteins/genetics/metabolism
;
Transcription Factors/genetics/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
