Identification of genes escaping X inactivation by allelic expression analysis in a novel hybrid mouse model.

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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].", "claims": [{"id": "claim-method", "statement": "To identify escape genes and estimate the statistical confidence of escape probability of X-linked genes, we developed the following binomial model.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:26693509", "locator": "sections[10] \"RNA-seq analysis and identification of escape genes\" paragraph 3", "quote": "To identify escape genes and estimate the statistical confidence of escape probability of X-linked genes, we developed the following binomial model."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data is publicly available through the GEO database under ascension numbers GSM1014171, GSE44255, and GSE59779.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:26693509", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The data is publicly available through the GEO database under ascension numbers GSM1014171, GSE44255, and GSE59779."}], "state": "complete"}, {"id": "claim-target-result", "statement": "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.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:26693509", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "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."}, {"asset": "source:pmid:26693509", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The data is publicly available through the GEO database under ascension numbers GSM1014171, GSE44255, and GSE59779."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "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.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:26693509"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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