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

doi:10.1016/j.xgen.2023.100462

The human Y and inactive X chromosomes similarly modulate autosomal gene expression

Cell Genom. 2024 Jan 10;4(1):100462. doi: 10.1016/j.xgen.2023.100462. Epub 2023 Dec 13.

Authors

Adrianna K San Roman¹, Helen Skaletsky², Alexander K Godfrey³, Neha V Bokil³, Levi Teitz³, Isani Singh⁴, Laura V Blanton¹, Daniel W Bellott¹, Tatyana Pyntikova¹, Julian Lange³, Natalia Koutseva¹, Jennifer F Hughes¹, Laura Brown², Sidaly Phou², Ashley Buscetta⁵, Paul Kruszka⁵, Nicole Banks⁶, Amalia Dutra⁷, Evgenia Pak⁷, Patricia C Lasutschinkow⁸, Colleen Keen⁸, Shanlee M Davis⁹, Angela E Lin¹⁰, Nicole R Tartaglia¹¹, Carole Samango-Sprouse¹², Maximilian Muenke⁵, David C Page¹³

Affiliations

¹ Whitehead Institute, Cambridge, MA 02142, USA.
² Whitehead Institute, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Whitehead Institute, Cambridge, MA 02142, USA.
³ Whitehead Institute, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁴ Whitehead Institute, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA.
⁵ Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁶ 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.
⁷ Cytogenetics and Microscopy Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁸ Focus Foundation, Davidsonville, MD 21035, USA.
⁹ Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
¹⁰ Medical Genetics, Massachusetts General for Children, Boston, MA 02114, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
¹¹ 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.
¹² 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.
¹³ 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. Electronic address: dcpage@wi.mit.edu.

Abstract

Somatic cells of human males and females have 45 chromosomes in common, including the "active" X chromosome. In males the 46^th 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.

Keywords: CRISPR; Klinefelter syndrome; Turner syndrome; X chromosome inactivation; aneuploidy; gene expression; sex chromosomes; sex differences; transcription factors.

MeSH terms

Chromosomes, Human, X / genetics
Female
Gene Expression / genetics
Humans
Male
Sex Chromosome Aberrations
Transcription Factors* / genetics
Y Chromosome*

Substances

Transcription Factors

Abstract

MeSH terms

Substances

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