The human inactive X chromosome modulates expression of the active X chromosome

• DOI: 10.1016/j.xgen.2023.100259
• Publication Date: 2023-02-08T15:40:35Z
• Authors: Adrianna K. San R...; Alexander K. Godfrey; Helen Skaletsky; Daniel W. Bellott; Abigail F. Groff; Hannah L. Harris; Laura V. Blanton; Jennifer F. Hughes; Laura Brown; Sidaly Phou; Ashley Buscetta; Paul Kruszka; Nicole Banks; Amalia Dutra; Evgenia Pak; Patricia C. Lasut...; Colleen Keen; Shanlee M. Davis; Nicole R. Tartaglia; Carole Samango-Sp...; Maximilian Muenke; David C. Page
• Keywords: sex differences; 0301 basic medicine; 0303 health sciences; sex chromosomes; QH426-470; RC31-1245; Article; 03 medical and health sciences; gene expression; turner syndrome; Genetics; aneuploidy; X chromosome inactivation; Internal medicine

The "inactive" X chromosome (Xi) has been assumed to have little impact, in trans, on the "active" (Xa). To test this, we quantified Xi and Xa gene expression individuals with one zero three Xis. Our linear modeling revealed modular transcriptomes significant Xi-driven changes for 38% (162/423) of expressed genes. By integrating allele-specific analyses, found that modulation transcript levels by contributes many these (≥121 genes). incorporating metrics evolutionary constraint, identified 10 genes most likely drive sex differences common disease aneuploidy syndromes. We conclude human chromosomes are regulated both cis, through Xi-wide transcriptional attenuation, positive or negative individual Xi. sum cis trans effects differs widely among