The Human Inactive X Chromosome Modulates Expression of the Active X Chromosome

Overview

Journal Cell Genom

Date 2023 Feb 23

PMID 36819663

Authors

Adrianna K San Roman

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 Lasutschinkow

Colleen Keen

Shanlee M Davis

Nicole R Tartaglia

Carole Samango-Sprouse

Maximilian Muenke

David C Page

Affiliations

Soon will be listed here.

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.

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