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

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)2359-2372
Number of pages14
JournalCell Reports
Volume18
Issue number10
DOIs
Publication statusPublished - 7 Mar 2017

Cite this

Dreijerink, K. M. A., Groner, A. C., Vos, E. S. M., Font-Tello, A., Gu, L., Chi, D., ... Brown, M. (2017). Enhancer-Mediated Oncogenic Function of the Menin Tumor Suppressor in Breast Cancer. Cell Reports, 18(10), 2359-2372. https://doi.org/10.1016/j.celrep.2017.02.025