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 journal/periodicalArticleScientificpeer-review

55 Citations (Scopus)

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 - 07 Mar 2017

Keywords

  • Breast Neoplasms
  • Cell Line, Tumor
  • Cell Proliferation
  • Enhancer Elements, Genetic
  • Estradiol
  • Estrogen Receptor alpha
  • Female
  • GATA3 Transcription Factor
  • Gene Expression Regulation, Neoplastic
  • Genomics
  • Hepatocyte Nuclear Factor 3-alpha
  • Histones
  • Humans
  • Lysine
  • Methylation
  • Oncogenes
  • Promoter Regions, Genetic
  • Protein Binding
  • Proto-Oncogene Proteins
  • Transcription, Genetic
  • Journal Article

Fingerprint

Dive into the research topics of 'Enhancer-Mediated Oncogenic Function of the Menin Tumor Suppressor in Breast Cancer'. Together they form a unique fingerprint.

Cite this