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Updated: Aug 9, 2025

Manipulation of Ploidy in Caenorhabditis elegans
Published on: March 15, 2018
Distinct dosage compensations of ploidy-sensitive and -insensitive X chromosome genes during development and in
Mengbiao Guo1, Zhengwen Fang1, Bohong Chen1
1Key Laboratory of Gene Engineering of the Ministry of Education, Institute of Healthy Aging Research, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, China.
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, TP53 and ATRX. 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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