The human inactive X chromosome modulates expression of the active X chromosome
Authors
Adrianna K. San Roman, Whitehead Institute, Cambridge, MA 02142, USA.
Alexander K. Godfrey, Whitehead Institute, Cambridge, MA 02142, USA.
Helen Skaletsky, Whitehead Institute, Cambridge, MA 02142, USA.
Daniel W. Bellott, Whitehead Institute, Cambridge, MA 02142, USA.
Abigail F. Groff, Whitehead Institute, Cambridge, MA 02142, USA.
Hannah L. Harris, Whitehead Institute, Cambridge, MA 02142, USA.
Laura V. Blanton, Whitehead Institute, Cambridge, MA 02142, USA.
Jennifer F. Hughes, Whitehead Institute, Cambridge, MA 02142, USA.
Laura Brown, Whitehead Institute, Cambridge, MA 02142, USA.
Sidaly Phou, Whitehead Institute, Cambridge, MA 02142, USA.
Ashley Buscetta, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Paul Kruszka, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Nicole Banks, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Amalia Dutra, Cytogenetics and Microscopy Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Evgenia Pak, Cytogenetics and Microscopy Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Patricia C. Lasutschinkow, Focus Foundation, Davidsonville, MD 21035, USA.
Colleen Keen, Focus Foundation, Davidsonville, MD 21035, USA.
Shanlee M. Davis, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Nicole R. Tartaglia, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Carole Samango-Sprouse, Focus Foundation, Davidsonville, MD 21035, USA.
Maximilian Muenke, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
David C. Page, Whitehead Institute, Cambridge, MA 02142, USA.
Document Type
Journal Article
Publication Date
2-8-2023
DOI
10.1016/j.xgen.2023.100259
Keywords
Klinefelter syndrome; X chromosome inactivation; aneuploidy; dosage sensitivity; gene expression; sex chromosomes; sex differences; turner syndrome
Abstract
The "inactive" X chromosome (Xi) has been assumed to have little impact, in , on the "active" X (Xa). To test this, we quantified Xi and Xa gene expression in individuals with one Xa and zero to three Xis. Our linear modeling revealed modular Xi and Xa transcriptomes and significant Xi-driven expression changes for 38% (162/423) of expressed X chromosome genes. By integrating allele-specific analyses, we found that modulation of Xa transcript levels by Xi contributes to many of these Xi-driven changes (≥121 genes). By incorporating metrics of evolutionary constraint, we identified 10 X chromosome genes most likely to drive sex differences in common disease and sex chromosome aneuploidy syndromes. We conclude that human X chromosomes are regulated both in , through Xi-wide transcriptional attenuation, and in , through positive or negative modulation of individual Xa genes by Xi. The sum of these and effects differs widely among genes.
APA Citation
San Roman, Adrianna K.; Godfrey, Alexander K.; Skaletsky, Helen; Bellott, Daniel W.; Groff, Abigail F.; Harris, Hannah L.; Blanton, Laura V.; Hughes, Jennifer F.; Brown, Laura; Phou, Sidaly; Buscetta, Ashley; Kruszka, Paul; Banks, Nicole; Dutra, Amalia; Pak, Evgenia; Lasutschinkow, Patricia C.; Keen, Colleen; Davis, Shanlee M.; Tartaglia, Nicole R.; Samango-Sprouse, Carole; Muenke, Maximilian; and Page, David C., "The human inactive X chromosome modulates expression of the active X chromosome" (2023). GW Authored Works. Paper 2426.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/2426
