2026-10-15T07:56:16Z https://data.mendeley.com/oai

oai:data.mendeley.com/w9dndxzmxj.2 2025-02-13T16:46:23Z

Gao, Chuan ZHX2 alters chromatin looping to drive cancer metastasis Mendeley Data Hypoxia and dysregulated phase separation can both activate oncogenic transcriptomic profiles, thus contributing to tumor progression. But whether hypoxia regulates transcription-associated phase separation remains unknown. Here, we find that the transcription factor, zinc fingers and homeoboxes 2 (ZHX2), undergoes phase separation under hypoxia, thus promoting its occupancy on chromatin and activating transcription for a cluster of oncogenes, that is enriched by metastatic genes distinct from targets of hypoxia-inducible factor (HIF) and pathologically relevant to breast cancer. Mechanistically, hypoxia induces phase separation of ZHX2 via a proline-rich intrinsically disordered region (IDR) in the nuclear localization sequence (NLS), thereby enhancing the phosphorylation of ZHX2 at S625 and S628 that incorporates CCCTC-binding factor (CTCF) in condensates to alter chromatin looping, consequently driving metastatic gene transcription and breast cancer metastasis. This fundamental mechanism provides significant insight into oncogene activation and suggests a phase separation-based therapeutic strategy for cancer. Cell Biology Dataset doi:10.17632/w9dndxzmxj.2 oai:data.mendeley.com/w9dndxzmxj.2 Creative Commons Attribution 4.0 International http://creativecommons.org/licenses/by/4.0 https://data.mendeley.com/datasets/w9dndxzmxj 2025-02-13T16:46:23Z