Cell Genomics (Jan 2024)
The human Y and inactive X chromosomes similarly modulate autosomal gene expression
- Adrianna K. San Roman,
- Helen Skaletsky,
- Alexander K. Godfrey,
- Neha V. Bokil,
- Levi Teitz,
- Isani Singh,
- Laura V. Blanton,
- Daniel W. Bellott,
- Tatyana Pyntikova,
- Julian Lange,
- Natalia Koutseva,
- Jennifer F. Hughes,
- Laura Brown,
- Sidaly Phou,
- Ashley Buscetta,
- Paul Kruszka,
- Nicole Banks,
- Amalia Dutra,
- Evgenia Pak,
- Patricia C. Lasutschinkow,
- Colleen Keen,
- Shanlee M. Davis,
- Angela E. Lin,
- Nicole R. Tartaglia,
- Carole Samango-Sprouse,
- Maximilian Muenke,
- David C. Page
Affiliations
- Adrianna K. San Roman
- Whitehead Institute, Cambridge, MA 02142, USA
- Helen Skaletsky
- Whitehead Institute, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Whitehead Institute, Cambridge, MA 02142, USA
- Alexander K. Godfrey
- Whitehead Institute, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
- Neha V. Bokil
- Whitehead Institute, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
- Levi Teitz
- Whitehead Institute, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
- Isani Singh
- Whitehead Institute, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA
- Laura V. Blanton
- Whitehead Institute, Cambridge, MA 02142, USA
- Daniel W. Bellott
- Whitehead Institute, Cambridge, MA 02142, USA
- Tatyana Pyntikova
- Whitehead Institute, Cambridge, MA 02142, USA
- Julian Lange
- Whitehead Institute, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
- Natalia Koutseva
- Whitehead Institute, Cambridge, MA 02142, USA
- Jennifer F. Hughes
- Whitehead Institute, Cambridge, MA 02142, USA
- Laura Brown
- Whitehead Institute, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Whitehead Institute, Cambridge, MA 02142, USA
- Sidaly Phou
- Whitehead Institute, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, 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; Eunice Kennedy Shriver National Institute of Child Health and Human Development, 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
- Angela E. Lin
- Medical Genetics, Massachusetts General for Children, Boston, MA 02114, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
- Nicole R. Tartaglia
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA; Developmental Pediatrics, eXtraOrdinarY Kids Program, Children’s Hospital Colorado, Aurora, CO 80011, USA
- Carole Samango-Sprouse
- Focus Foundation, Davidsonville, MD 21035, USA; Department of Pediatrics, George Washington University, Washington, DC 20052, USA; Department of Human and Molecular Genetics, Florida International University, Miami, FL 33199, 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; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Whitehead Institute, Cambridge, MA 02142, USA; Corresponding author
- Journal volume & issue
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Vol. 4,
no. 1
p. 100462
Abstract
Summary: Somatic cells of human males and females have 45 chromosomes in common, including the “active” X chromosome. In males the 46th chromosome is a Y; in females it is an “inactive” X (Xi). Through linear modeling of autosomal gene expression in cells from individuals with zero to three Xi and zero to four Y chromosomes, we found that Xi and Y impact autosomal expression broadly and with remarkably similar effects. Studying sex chromosome structural anomalies, promoters of Xi- and Y-responsive genes, and CRISPR inhibition, we traced part of this shared effect to homologous transcription factors—ZFX and ZFY—encoded by Chr X and Y. This demonstrates sex-shared mechanisms by which Xi and Y modulate autosomal expression. Combined with earlier analyses of sex-linked gene expression, our studies show that 21% of all genes expressed in lymphoblastoid cells or fibroblasts change expression significantly in response to Xi or Y chromosomes.
