Extensive Variation in Chromatin States Across Humans

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 individ...

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Bibliographic Details
Main Authors: 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
Other Authors: Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Format: Article
Language:en_US
Published: American Association for the Advancement of Science (AAAS) 2016
Online Access:http://hdl.handle.net/1721.1/100726
Description
Summary: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.