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Landscape of X chromosome inactivation across human tissues.

Publication ,  Journal Article
Tukiainen, T; Villani, A-C; Yen, A; Rivas, MA; Marshall, JL; Satija, R; Aguirre, M; Gauthier, L; Fleharty, M; Kirby, A; Cummings, BB; Aguet, F ...
Published in: Nature
October 2017

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.

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Published In

Nature

DOI

EISSN

1476-4687

ISSN

0028-0836

Publication Date

October 2017

Volume

550

Issue

7675

Start / End Page

244 / 248

Related Subject Headings

  • X Chromosome Inactivation
  • Transcriptome
  • Single-Cell Analysis
  • Sequence Analysis, RNA
  • Phenotype
  • Organ Specificity
  • Male
  • Humans
  • Genomics
  • Genome, Human
 

Citation

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MLA
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Tukiainen, T., Villani, A.-C., Yen, A., Rivas, M. A., Marshall, J. L., Satija, R., … MacArthur, D. G. (2017). Landscape of X chromosome inactivation across human tissues. Nature, 550(7675), 244–248. https://doi.org/10.1038/nature24265
Tukiainen, Taru, Alexandra-Chloé Villani, Angela Yen, Manuel A. Rivas, Jamie L. Marshall, Rahul Satija, Matt Aguirre, et al. “Landscape of X chromosome inactivation across human tissues.Nature 550, no. 7675 (October 2017): 244–48. https://doi.org/10.1038/nature24265.
Tukiainen T, Villani A-C, Yen A, Rivas MA, Marshall JL, Satija R, et al. Landscape of X chromosome inactivation across human tissues. Nature. 2017 Oct;550(7675):244–8.
Tukiainen, Taru, et al. “Landscape of X chromosome inactivation across human tissues.Nature, vol. 550, no. 7675, Oct. 2017, pp. 244–48. Epmc, doi:10.1038/nature24265.
Tukiainen T, Villani A-C, Yen A, Rivas MA, Marshall JL, Satija R, Aguirre M, Gauthier L, Fleharty M, Kirby A, Cummings BB, Castel SE, Karczewski KJ, Aguet F, Byrnes A, GTEx Consortium, Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group, Statistical Methods groups—Analysis Working Group, Enhancing GTEx (eGTEx) groups, NIH Common Fund, NIH/NCI, NIH/NHGRI, NIH/NIMH, NIH/NIDA, Biospecimen Collection Source Site—NDRI, Biospecimen Collection Source Site—RPCI, Biospecimen Core Resource—VARI, Brain Bank Repository—University of Miami Brain Endowment Bank, Leidos Biomedical—Project Management, ELSI Study, Genome Browser Data Integration &Visualization—EBI, Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz, Lappalainen T, Regev A, Ardlie KG, Hacohen N, MacArthur DG. Landscape of X chromosome inactivation across human tissues. Nature. 2017 Oct;550(7675):244–248.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

ISSN

0028-0836

Publication Date

October 2017

Volume

550

Issue

7675

Start / End Page

244 / 248

Related Subject Headings

  • X Chromosome Inactivation
  • Transcriptome
  • Single-Cell Analysis
  • Sequence Analysis, RNA
  • Phenotype
  • Organ Specificity
  • Male
  • Humans
  • Genomics
  • Genome, Human