title: Identification of genes escaping X inactivation by allelic expression analysis in a novel hybrid mouse model.
abstract: X chromosome inactivation (XCI) is a female-specific mechanism that serves to balance gene dosage between the sexes whereby one X chromosome in females is inactivated during early development. Despite this silencing, a small portion of genes escape inactivation and remain expressed from the inactive X (Xi). Little is known about the distribution of escape from XCI in different tissues in vivo and about the mechanisms that control tissue-specific differences. Using a new binomial model in conjunction with a mouse model with identifiable alleles and skewed X inactivation we are able to survey genes that escape XCI in vivo. We show that escape from X inactivation can be a common feature of some genes, whereas others escape in a tissue specific manner. Furthermore, we characterize the chromatin environment of escape genes and show that expression from the Xi correlates with factors associated with open chromatin and that CTCF co-localizes with escape genes. Here, we provide a detailed description of the experimental design and data analysis pipeline we used to assay allele-specific expression and epigenetic characteristics of genes escaping X inactivation. The data is publicly available through the GEO database under ascension numbers GSM1014171, GSE44255, and GSE59779. Interpretation and discussion of these data are included in a previously published study (Berletch et al., 2015) [1].
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, USA.
authors.forename: Joel B
authors.initials: JB
authors.lastname: Berletch
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Wenxiu
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Shendure
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA, USA.
authors.forename: William S
authors.initials: WS
authors.lastname: Noble
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, USA ; Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Disteche
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, USA.
authors.forename: Xinxian
authors.initials: X
authors.lastname: Deng
keywords: Allele-specific; ChIP-seq; Gene expression; RNA-seq; Transcription factor; X inactivation