Landscape of X chromosome inactivation across human tissues

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Tukiainen, T (Author) Other; Villani, A (Author) Other; Yen, A (Author) Other; Rivas, MA (Author) Other; Marshall, JL (Author) Other; Satija, R (Author) Other; Aguirre, M (Author) Other; Gauthier, L (Author) Other; Fleharty, M (Author) Other; Kirby, A (Author) Other; Cummings, BB (Author) Other; Castel, SE (Author) Other; Karczewski, KJ (Author) Other; Aguet, F (Author) Other; Byrnes, A (Author) Other; Aguet, F (Author) Other; Ardlie, KG (Author) Other; Cummings, BB (Author) Other; Gelfand, ET (Author) Other; Getz, G (Author) Other; Hadley, K (Author) Other; Handsaker, RE (Author) Other; Huang, KH (Author) Other; Kashin, S (Author) Other; Karczewski, KJ (Author) Other; Lek, M (Author) Other; Li, X (Author) Other; MacArthur, DG (Author) Other; Nedzel, JL (Author) Other; Nguyen, DT (Author) Other; Noble, MS (Author) Other; Segrè, AV (Author) Other; Trowbridge, CA (Author) Other; Tukiainen, T (Author) Other; Abell, NS (Author) Other; Balliu, B (Author) Other; Barshir, R (Author) Other; Basha, O (Author) Other; Battle, A (Author) Other; Bogu, GK (Author) Other; Brown, A (Author) Other; Brown, CD (Author) Other; Castel, SE (Author) Other; Chen, LS (Author) Other; Chiang, C (Author) Other; Conrad, DF (Author) Other; Cox, NJ (Author) Other; Damani, FN (Author) Other; Davis, JR (Author) Other; Delaneau, O (Author) Other; Dermitzakis, ET (Author) Other; Engelhardt, BE (Author) Other; Eskin, E (Author) Other; Ferreira, PG (Author) Other; Frésard, L (Author) Other; Gamazon, ER (Author) Other; Garrido-Martín, D (Author) Other; Gewirtz, ADH (Author) Other; Gliner, G (Author) Other; Gloudemans, MJ (Author) Other; Guigo, R (Author) Other; Hall, IM (Author) Other; Han, B (Author) Other; He, Y (Author) Other; Hormozdiari, F (Author) Other; Howald, C (Author) Other; Kyung Im, H (Author) Other; Jo, B (Author) Other; Yong Kang, E (Author) Other; Kim, Y (Author) Other; Kim-Hellmuth, S (Author) Other; Lappalainen, T (Author) Other; Li, G (Author) Other; Li, X (Author) Other; Liu, B (Author) Other; Mangul, S (Author) Other; McCarthy, MI (Author) Other; McDowell, IC (Author) Other; Mohammadi, P (Author) Other; Monlong, J (Author) Other; Montgomery, SB (Author) Other; Muñoz-Aguirre, M (Author) Other; Ndungu, AW (Author) Other; Nicolae, DL (Author) Other; Nobel, AB (Author) Other; Oliva, M (Author) Other; Ongen, H (Author) Other; Palowitch, JJ (Author) Other; Panousis, N (Author) Other; Papasaikas, P (Author) Other; Park, Y (Author) Other; Parsana, P (Author) Other; Payne, AJ (Author) Other; Peterson, CB (Author) Other; Quan, J (Author) Other; Reverter, F (Author) Other; Sabatti, C (Author) Other; Saha, A (Author) Other; Sammeth, M (Author) Other; Scott, AJ (Author) Other; Shabalin, AA (Author) Other; Sodaei, R (Author) Other; Stephens, M (Author) Other; Stranger, BE (Author) Other; Strober, BJ (Author) Other; Sul, JH (Author) Other; Tsang, EK (Author) Other; Urbut, S (Author) Other; van de Bunt, M (Author) Other; Wang, G (Author) Other; Wen, X (Author) Other; Wright, FA (Author) Other; Xi, HS (Author) Other; Yeger-Lotem, E (Author) Other; Zappala, Z (Author) Other; Zaugg, JB (Author) Other; Zhou, Y (Author) Other; Akey, JM (Author) Other; Bates, D (Author) Other; Chan, J (Author) Other; Chen, LS (Author) Other; Claussnitzer, M (Author) Other; Demanelis, K (Author) Other; Diegel, M (Author) Other; Doherty, JA (Author) Other; Feinberg, AP (Author) Other; Fernando, MS (Author) Other; Halow, J (Author) Other; Hansen, KD (Author) Other; Haugen, E (Author) Other; Hickey, PF (Author) Other; Hou, L (Author) Other; Jasmine, F (Author) Other; Jian, R (Author) Other; Jiang, L (Author) Other; Johnson, A (Author) Other; Kaul, R (Author) Other; Kellis, M (Author) Other; Kibriya, MG (Author) Other; Lee, K (Author) Other; Li, JB (Author) Other; Li, Q (Author) Other; Li, X (Author) Other; Lin, J (Author) Other; Lin, S (Author) Other; Linder, S (Author) Other; Linke, C (Author) Other; Liu, Y (Author) Other; Maurano, MT (Author) Other; Molinie, B (Author) Other; Montgomery, SB (Author) Other; Nelson, J (Author) Other; Neri, FJ (Author) Other; Oliva, M (Author) Other; Park, Y (Author) Other; Pierce, BL (Author) Other; Rinaldi, NJ (Author) Other; Rizzardi, LF (Author) Other; Sandstrom, R (Author) Other; Skol, A (Author) Other; Smith, KS (Author) Other; Snyder, MP (Author) Other; Stamatoyannopoulos, J (Author) Other; Stranger, BE (Author) Other; Tang, H (Author) Other; Tsang, EK (Author) Other; Wang, L (Author) Other; Wang, M (Author) Other; Van Wittenberghe, N (Author) Other; Wu, F (Author) Other; Zhang, R (Author) Other; Nierras, CR (Author) Other; Branton, PA (Author) Other; Carithers, LJ (Author) Other; Guan, P (Author) Other; Moore, HM (Author) Other; Rao, A (Author) Other; Vaught, JB (Author) Other; Gould, SE (Author) Other; Lockart, NC (Author) Other; Martin, C (Author) Other; Struewing, JP (Author) Other; Volpi, S (Author) Other; Addington, AM (Author) Other; Koester, SE (Author) Other; Little, AR (Author) Other; Brigham, LE (Author) Other; Hasz, R (Author) Other; Hunter, M (Author) Other; Johns, C (Author) Other; Johnson, M (Author) Other; Kopen, G (Author) Other; Leinweber, WF (Author) Other; Lonsdale, JT (Author) Other; McDonald, A (Author) Other; Mestichelli, B (Author) Other; Myer, K (Author) Other; Roe, B (Author) Other; Salvatore, M (Author) Other; Shad, S (Author) Other; Thomas, JA (Author) Other; Walters, G (Author) Other; Washington, M (Author) Other; Wheeler, J (Author) Other; Bridge, J (Author) Other; Foster, BA (Author) Other; Gillard, BM (Author) Other; Karasik, E (Author) Other; Kumar, R (Author) Other; Miklos, M (Author) Other; Moser, MT (Author) Other; Jewell, SD (Author) Other; Montroy, RG (Author) Other; Rohrer, DC (Author) Other; Valley, DR (Author) Other; Davis, DA (Author) Other; Mash, DC (Author) Other; Undale, AH (Author) Other; Smith, AM (Author) Other; Tabor, DE (Author) Other; Roche, NV (Author) Other; McLean, JA (Author) Other; Vatanian, N (Author) Other; Robinson, KL (Author) Other; Sobin, L (Author) Other; Barcus, ME (Author) Other; Valentino, KM (Author) Other; Qi, L (Author) Other; Hunter, S (Author) Other; Hariharan, P (Author) Other; Singh, S (Author) Other; Um, KS (Author) Other; Matose, T (Author) Other; Tomaszewski, MM (Author) Other; Barker, LK (Author) Other; Mosavel, M (Author) Other; Siminoff, LA (Author) Other; Traino, HM (Author) Other; Flicek, P (Author) Other; Juettemann, T (Author) Other; Ruffier, M (Author) Other; Sheppard, D (Author) Other; Taylor, K (Author) Other; Trevanion, SJ (Author) Other; Zerbino, DR (Author) Other; Craft, B (Author) Other; Goldman, M (Author) Other; Haeussler, M (Author) Other; Kent, WJ (Author) Other; Lee, CM (Author) Other; Paten, B (Author) Other; Rosenbloom, KR (Author) Other; Vivian, J (Author) Other; Zhu, J (Author) Other; Lappalainen, T (Author) Other; Regev, A (Author) Other; Ardlie, KG (Author) Other; Hacohen, N (Author) Other; MacArthur, DG (Author) Other

Journal

Title: Nature

Vol. 550

Pages: 244-248

ISSN: 0028-0836

Publisher: Springer Nature

Indexing

Scopus - 324 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

CORDIS: Natural sciences > Biological sciences > Biology > Computational biology

FOS: Natural sciences > Computer and information sciences

Other information

Authenticus ID: P-00Q-55M

DOI: 10.1038/nature24265

Abstract (EN): 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 individuals1,2. The extent to which XCI is shared between cells and tissues remains poorly characterized3,4, as does the degree to which incomplete XCI manifests as detectable sex differences in gene expression5 and phenotypic traits6. 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 diversity6,7. 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.

Language: English

Type (Professor's evaluation): Scientific