title: Chromatin signature of widespread monoallelic expression.
abstract: In 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.01256.001.
authors.affiliation: Department of Cancer Biology and Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Boston, United States.
authors.forename: Anwesha
authors.initials: A
authors.lastname: Nag
authors.forename: Virginia
authors.initials: V
authors.lastname: Savova
authors.forename: Ho-Lim
authors.initials: HL
authors.lastname: Fung
authors.forename: Alexander
authors.initials: A
authors.lastname: Miron
authors.forename: Guo-Cheng
authors.initials: GC
authors.lastname: Yuan
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Gimelbrant
mesh_terms: D000483:Alleles; D002843:Chromatin / Q000235:genetics*; D020868:Gene Silencing; D006801:Humans; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin
keywords: AST-Seq; bivalent; chromatin; epigenome; monoallelic expression