An EZH2-NF-κB regulatory axis drives expression of pro-oncogenic gene signatures in triple negative breast cancer.

ABSTRACT: The histone methyltransferase EZH2 has been studied most extensively in the context of PRC2-dependent gene repression. Accumulating evidence indicates non-canonical functions for EZH2 in cancer contexts including promoting paradoxical gene expression through interactions with transcription factors, including NF-κB in triple negative breast cancer (TNBC). We profile EZH2 and NF-κB factor co-localization and positive gene regulation genome-wide, and define a subset of NF-κB targets and genes associated with oncogenic functions in TNBC that is enriched in patient datasets. We demonstrate interaction between EZH2 and RelA requiring the recently identified transactivation domain (TAD) which mediates EZH2 recruitment to, and activation of certain NF-κB-dependent genes, and supports downstream mi

SUBMITTER: Dardis GJ 

PROVIDER: S-EPMC10319845 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature