Nag, AnweshaSavova, VirginiaFung, Ho-LimMiron, AlexanderYuan, Guo-ChengZhang, KunGimelbrant, Alexander2014-03-112013Nag, Anwesha, Virginia Savova, Ho-Lim Fung, Alexander Miron, Guo-Cheng Yuan, Kun Zhang, and Alexander A Gimelbrant. 2013. “Chromatin signature of widespread monoallelic expression.” eLife 2 (1): e01256. doi:10.7554/eLife.01256. http://dx.doi.org/10.7554/eLife.01256.2050-084Xhttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11879703In mammals, numerous autosomal genes are subject to mitotically stable monoallelic expression (MAE), including genes that play critical roles in a variety of human diseases. Due to challenges posed by the clonal nature of MAE, very little is known about its regulation; in particular, no molecular features have been specifically linked to MAE. In this study, we report an approach that distinguishes MAE genes in human cells with great accuracy: a chromatin signature consisting of chromatin marks associated with active transcription (H3K36me3) and silencing (H3K27me3) simultaneously occurring in the gene body. The MAE signature is present in ∼20% of ubiquitously expressed genes and over 30% of tissue-specific genes across cell types. Notably, it is enriched among key developmental genes that have bivalent chromatin structure in pluripotent cells. Our results open a new approach to the study of MAE that is independent of polymorphisms, and suggest that MAE is linked to cell differentiation. DOI: http://dx.doi.org/10.7554/eLife.01256.001en-USmonoallelic expressionchromatinepigenomebivalentAST-SeqHumanJournal Article2014-03-1110.7554/eLife.01256