@article{f64cbb5fa6c644cea6b7a6c3dd5a998f,
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 Neoplasms/genetics, Cell Line, Tumor, Cell Proliferation, Enhancer Elements, Genetic/genetics, Estradiol/pharmacology, Estrogen Receptor alpha/metabolism, Female, GATA3 Transcription Factor/metabolism, Gene Expression Regulation, Neoplastic, Genomics, Hepatocyte Nuclear Factor 3-alpha/metabolism, Histones/metabolism, Humans, Lysine/metabolism, Methylation, Oncogenes, Promoter Regions, Genetic, Protein Binding/drug effects, Proto-Oncogene Proteins/genetics, Transcription, Genetic",
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 = "Copyright {\textcopyright} 2017 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2017",
month = mar,
day = "7",
doi = "10.1016/j.celrep.2017.02.025",
language = "English",
volume = "18",
pages = "2359--2372",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "10",
}