Whole RNA-seq on clones of GM12878 lymphoblastoid clones DF1 and DF2

Analysis of Allelic bias in clonal lymphoblastoid cells. 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. Here 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. Overall design: Poly A purified total RNA was used for library construction using a method described by Parkhomchuk et. al. NAR 2009. The library was strand-specific but the pipeline for data analysis does not assume the library is strand-specific.

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Nag A, Savova V, Fung HL, Miron A, Yuan GC, Zhang K, Gimelbrant AA