CREPT is required for the metastasis of triple-negative breast cancer through a co-operational-chromatin loop-based gene regulation.

ABSTRACT: Triple-negative breast cancer (TNBC) is recognized for its aggressiveness, yet the mechanism underlying metastasis remains unclear. Here, we report that CREPT/RPRD1B, which exhibits somatic gene copy-number amplifications and elevated expression, correlates with poor patient survival and drives TNBC metastasis. We demonstrate that CREPT alters three-dimensional genome structures in topologically-associating domain (TAD) status and chromatin loops via occupying promoters and enhancers. Specifically, CREPT mediates 1082 co-operational chromatin loops configured by enhancer-promoter and promoter-termination loops, which are validated by HiChIP analyses and visualized by Tn5-FISH experiments. These loops orchestrate RNAPII loading and recycling to enhance the metastatic gene expression. Disrup

SUBMITTER: Li J 

PROVIDER: S-EPMC12150493 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature