Enhancer-Mediated Oncogenic Function of the Menin Tumor Suppressor in Breast Cancer.

ABSTRACT: While the multiple endocrine neoplasia type 1 (MEN1) gene functions as a tumor suppressor in a variety of cancer types, we explored its oncogenic role in breast tumorigenesis. The MEN1 gene product menin is involved in H3K4 trimethylation and co-activates transcription. We integrated ChIP-seq and RNA-seq data to identify menin target genes. Our analysis revealed that menin-dependent target gene promoters display looping to distal enhancers that are bound by menin, FOXA1 and GATA3. In this fashion, MEN1 co-regulates a proliferative breast cancer-specific gene expression program in ER⁺ cells. In primary mammary cells, MEN1 exerts an anti-proliferative function by regulating a distinct expression signature. Our findings clarify the cell-type-specific functions of MEN1 and inform th

SUBMITTER: Dreijerink KMA 

PROVIDER: S-EPMC5609449 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature