Journal
CELL REPORTS
Volume 18, Issue 10, Pages 2359-2372Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2017.02.025
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Funding
- Dutch Cancer Society [UU 2012-5370]
- Swiss National Science Foundation [P300P3_151145]
- NBCF practitioner fellowship [PRAC14-02]
- Novartis
- Swiss National Science Foundation (SNF) [P300P3_151145] Funding Source: Swiss National Science Foundation (SNF)
- National Breast Cancer Foundation [PRAC-14-002] Funding Source: researchfish
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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.
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