Chromatin signature of widespread monoallelic expression
نویسندگان
چکیده
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.
منابع مشابه
Chromatin Signature Identifies Monoallelic Gene Expression Across Mammalian Cell Types
Monoallelic expression of autosomal genes (MAE) is a widespread epigenetic phenomenon which is poorly understood, due in part to current limitations of genome-wide approaches for assessing it. Recently, we reported that a specific histone modification signature is strongly associated with MAE and demonstrated that it can serve as a proxy of MAE in human lymphoblastoid cells. Here, we use murine...
متن کاملAn Epigenetic Signature for Monoallelic Olfactory Receptor Expression
Constitutive heterochromatin is traditionally viewed as the static form of heterochromatin that silences pericentromeric and telomeric repeats in a cell cycle- and differentiation-independent manner. Here, we show that, in the mouse olfactory epithelium, olfactory receptor (OR) genes are marked in a highly dynamic fashion with the molecular hallmarks of constitutive heterochromatin, H3K9me3 and...
متن کاملWidespread monoallelic expression on human autosomes.
Monoallelic expression with random choice between the maternal and paternal alleles defines an unusual class of genes comprising X-inactivated genes and a few autosomal gene families. Using a genome-wide approach, we assessed allele-specific transcription of about 4000 human genes in clonal cell lines and found that more than 300 were subject to random monoallelic expression. For a majority of ...
متن کاملNoncoding RNAs and Intranuclear Positioning in Monoallelic Gene Expression
Mammalian X inactivation, imprinting, and allelic exclusion are classic examples of monoallelic gene expression. Two emerging themes are thought to be critical for monoallelic expression: (1) noncoding, often antisense, transcription linked to differential chromatin marks on otherwise homologous alleles and (2) physical segregation of alleles to separate domains within the nucleus. Here, we hig...
متن کاملPerspective: Is Random Monoallelic Expression a Contributor to Phenotypic Variability of Autosomal Dominant Disorders?
Several factors have been proposed as contributors to interfamilial and intrafamilial phenotypic variability in autosomal dominant disorders, including allelic variation, modifier genes, environmental factors and complex genetic and environmental interactions. However, regardless of the similarity of genetic background and environmental factors, asymmetric limb or trunk anomalies in a single in...
متن کامل