Distinct Dosage Compensations of Ploidy-sensitive and -insensitive X Chromosome Genes During Development and in Diseases

Overview

Journal iScience

Publisher Cell Press

Date 2023 Feb 17

PMID 36798435

Authors

Mengbiao Guo

Zhengwen Fang

Bohong Chen

Zhou Songyang

Yuanyan Xiong

Affiliations

Soon will be listed here.

Abstract

The active X chromosome in mammals is upregulated to balance its dosage to autosomes during evolution. However, it is elusive why the known dosage compensation machinery showed uneven and small influence on X genes. Here, based on >20,000 transcriptomes, we identified two X gene groups (ploidy-sensitive [PSX] and ploidy-insensitive [PIX]), showing distinct but evolutionarily conserved dosage compensations (termed XAR). We demonstrated that XAR-PIX was downregulated whereas XAR-PSX upregulated at both RNA and protein levels across cancer types, in contrast with their trends during stem cell differentiation. XAR-PIX, but not XAR-PSX, was lower and correlated with autoantibodies and inflammation in patients of lupus, suggesting that insufficient dosage of PIX genes contribute to lupus pathogenesis. We further identified and experimentally validated two XAR regulators, and . Collectively, we provided insights into X dosage compensation in mammals and demonstrated different regulation of PSX and PIX and their pathophysiological roles in human diseases.

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