Authors
Xiaoli Xie, Delin Tan, Jingyun Mo, Yang Xu, Qingqiang Ni, Ting Liu, Huaiming Wang, Bingjie Chen, Yujia Liao, Yingnan Lin, Wanting Chen, Susu Luo, Qing Fang, Menglan Zhao, Yangyinhui Yu, Cunjing Zheng, Ruolin Cui, Jiaying Wang, Hong Chang, Qing Gong, Alfred Sze-Lok Cheng, Huiqing Jiang, Tingting Li, Jia Wang
Published in
Nature cell biology. Sep 11, 2026. Epub Sep 11, 2026.
Abstract
Changes of three-dimensional chromosome organization in cancers are well established, but little focus has been placed on the behaviour of X chromosome (chrX). Here we show that hepatic chrX of male mice exhibits chromosome segregation, which is attenuated during hepatocellular carcinoma (HCC) development. Using F1 hybrid mice, we find that both conformation change and gene activation on male active chrX (Xa) are more pronounced than those on female Xa, which is correlated with male bias in liver diseases. Of note, analysis of human hepatic tissues demonstrates that normal Xa possesses a bipartite mega-domain structure, which is dissolved in fibrotic and HCC tissues across both sexes. This bipartite Xa is liver-specific, and shows little correlation with ploidy status. Furthermore, deletion of the megabase-scale Xa boundary via CRISPR-Cas3 disrupts the bipartite Xa conformation and drives a premalignant transition. Together, this comprehensive analysis highlights a key role of Xa conformation change in promoting HCC development.
PMID:
42728307
Bibliographic data and abstract were imported from PubMed on 12 Sep 2026.
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