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

Koen M A Dreijerink, Anna C Groner, Erica S M Vos, Alba Font-Tello, Lei Gu, David Chi, Jaime Reyes, Jennifer Cook, Elgene Lim, Charles Y Lin, Wouter de Laat, Prakash K Rao, Henry W Long, Myles Brown

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)2359-2372
Aantal pagina's14
TijdschriftCell Reports
Volume18
Nummer van het tijdschrift10
DOI's
StatusGepubliceerd - 07 mrt 2017

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