Epigenetic Regulation of Chromosomal Instability by EZH2 Methyltransferase.

ABSTRACT: Chromosomal instability (CIN) and epigenetic reprogramming are central drivers of breast cancer progression, yet the mechanisms connecting them remain elusive. Here, we uncover a direct role for EZH2 histone methyltransferase in promoting CIN in triple-negative breast cancer. Across breast cancers, EZH2 expression correlates with copy-number alterations, and its catalytic activity is associated with increased CIN in metastasis-initiating cells. Pharmacologic EZH2 inhibition suppresses CIN, revealing an unexpected vulnerability. Integrated chromatin and transcriptome profiling identified tankyrase (TNKS), a PARP, as a direct transcriptional target of EZH2. Mechanistically, EZH2-mediated TNKS suppression disrupts centrosomal P4.1-associated protein (CPAP), driving centrosome overduplication,

SUBMITTER: Bai Y 

PROVIDER: S-EPMC12768130 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature