Welcome to the UPF Digital Repository

Landscape of X chromosome inactivation across human tissues

Show simple item record

dc.contributor.author Tukiainen, Taru
dc.contributor.author Guigó Serra, Roderic
dc.contributor.author MacArthur, Daniel G.
dc.contributor.author Genotype-Tissue Expression (GTEx) Consortium
dc.date.accessioned 2018-03-19T14:33:48Z
dc.date.available 2018-03-19T14:33:48Z
dc.date.issued 2017
dc.identifier.citation Tukiainen T, Villani AC, Yen A, Rivas MA, Marshall JL, Satija R et al. Landscape of X chromosome inactivation across human tissues. Nature. 2017 Oct 11;550(7675):244-248. DOI: 10.1038/nature24265
dc.identifier.issn 0028-0836
dc.identifier.uri http://hdl.handle.net/10230/34204
dc.description.abstract X chromosome inactivation (XCI) silences transcription from one of the two X chromosomes in female mammalian cells to balance expression dosage between XX females and XY males. XCI is, however, incomplete in humans: up to one-third of X-chromosomal genes are expressed from both the active and inactive X chromosomes (Xa and Xi, respectively) in female cells, with the degree of 'escape' from inactivation varying between genes and individuals. The extent to which XCI is shared between cells and tissues remains poorly characterized, as does the degree to which incomplete XCI manifests as detectable sex differences in gene expression and phenotypic traits. Here we describe a systematic survey of XCI, integrating over 5,500 transcriptomes from 449 individuals spanning 29 tissues from GTEx (v6p release) and 940 single-cell transcriptomes, combined with genomic sequence data. We show that XCI at 683 X-chromosomal genes is generally uniform across human tissues, but identify examples of heterogeneity between tissues, individuals and cells. We show that incomplete XCI affects at least 23% of X-chromosomal genes, identify seven genes that escape XCI with support from multiple lines of evidence and demonstrate that escape from XCI results in sex biases in gene expression, establishing incomplete XCI as a mechanism that is likely to introduce phenotypic diversity. Overall, this updated catalogue of XCI across human tissues helps to increase our understanding of the extent and impact of the incompleteness in the maintenance of XCI.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Nature Publishing Group
dc.relation.ispartof Nature. 2017 Oct 11;550(7675):244-248
dc.rights © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) licence. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons licence, users will need to obtain permission from the licence holder to reproduce the material. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Landscape of X chromosome inactivation across human tissues
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/nature24265
dc.subject.keyword Dosage compensation
dc.subject.keyword Epidemiology
dc.subject.keyword Genetics research
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


This item appears in the following Collection(s)

Show simple item record

Search DSpace


Advanced Search

Browse

My Account

Statistics

Compliant to Partaking