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

San Roman, A.K., Skaletsky, H., Godfrey, A.K., Bokil, N.V., Teitz, L., Singh, I., Blanton, L.V., Bellott, D.W., Pyntikova, T., Lange, J., Koutseva, N., Hughes, J.F., Brown, L., Phou, S., Buscetta, A., Kruszka, P., Banks, N., Dutra, A., Pak, E., Lasutschinkow, P.C., Keen, C., Davis, S.M., Lin, A.E., Tartaglia, N.R., Samango-Sprouse, C., Muenke, M., Page, D.C. (2024) Cell Genomics 4(1): 100462.

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Abstract: 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.

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