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 the development of menin-directed treatments for breast cancer. Show more
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https://doi.org/10.3929/ethz-b-000191576Publication status
publishedExternal links
Journal / series
Cell ReportsVolume
Pages / Article No.
Publisher
ElsevierSubject
breast cancer; MEN1; Tumor Suppressor; oncogene; transcription; epigenetics; menin; histone H3K4 trimethylation; enhancerMore
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