@article{a2a75d4d7a40495482bd298b6477d25d,
title = "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.",
keywords = "breast cancer, enhancer, epigenetics, histone H3K4 trimethylation, MEN1, menin, oncogene, transcription, tumor suppressor",
author = "Dreijerink, {Koen M A} and Groner, {Anna C.} and Vos, {Erica S M} and Alba Font-Tello and Lei Gu and David Chi and Jaime Reyes and Jennifer Cook and Elgene Lim and Lin, {Charles Y.} and {de Laat}, Wouter and Rao, {Prakash K.} and Long, {Henry W.} and Myles Brown",
note = "Funding Information: We thank the members of the Brown lab and the Center for Functional Cancer Epigenetics for useful discussion and feedback, especially Gilles Buchwalter, Laura Cato, Tom Westerling, Shengen Shawn Hu, Xintao Qiu, and Fugen Li and also Marc Timmers at the UMC Utrecht. We thank John Daley III from the DFCI Flow Cytometry Facility for technical advice. K.M.A.D. is supported by the Dutch Cancer Society (UU 2012-5370). A.C.G. is funded by an Advanced Postdoc. Mobility fellowship from the Swiss National Science Foundation (P300P3_151145). E.L. is supported through Love Your Sister and an NBCF practitioner fellowship (PRAC14-02). M.B. receives sponsored research support from Novartis and is a consultant to Novartis in the area of cancer epigenetics. Publisher Copyright: {\textcopyright} 2017 The Author(s)",
year = "2017",
month = mar,
day = "7",
doi = "10.1016/j.celrep.2017.02.025",
language = "English",
volume = "18",
pages = "2359--2372",
journal = "Cell Reports [E]",
issn = "2211-1247",
publisher = "Cell Press",
number = "10",
}