Epigenetic reprogramming of a distal developmental enhancer cluster drives SOX2 overexpression in breast and lung adenocarcinoma.

ABSTRACT: Enhancer reprogramming has been proposed as a key source of transcriptional dysregulation during tumorigenesis, but the molecular mechanisms underlying this process remain unclear. Here, we identify an enhancer cluster required for normal development that is aberrantly activated in breast and lung adenocarcinoma. Deletion of the SRR124-134 cluster disrupts expression of the SOX2 oncogene, dysregulates genome-wide transcription and chromatin accessibility and reduces the ability of cancer cells to form colonies in vitro. Analysis of primary tumors reveals a correlation between chromatin accessibility at this cluster and SOX2 overexpression in breast and lung cancer patients. We demonstrate that FOXA1 is an activator and NFIB is a repressor of SRR124-134 activity and SOX2 transcription in ca

SUBMITTER: Abatti LE 

PROVIDER: S-EPMC10602899 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature