Dissecting an Estrogen Receptor-Regulated Enhancer Code in Breast Cancer

Abstract

The functional importance of gene enhancers in regulated gene expression is well established and recent evidence indicates that, in addition to widespread transcription of long non-coding RNA (ncRNA) transcripts in mammalian cells, bidirectional ncRNAs, referred to as eRNAs, are present on enhancer, However, it has remained unclear whether these eRNAs are functional, or merely a reflection of enhancer activation and may be a cause of upregulation of cancer genes. We found that breast cancer causing,17 -estradiol (E2)-bound estrogen receptor (ER ) on enhancers causes a global upregulation of eRNA transcription in enhancers adjacent to E2 upregulated coding genes in MCF-7 (Breast cancer cells). These induced eRNAs are required for the observed induction of target coding genes, causing the increased strength of specific enhancer:promoter looping, Our data indicate that eRNAs induced by liganded ER are required for effective recruitment of critical machinery required for estrogen regulated coding gene activation events and suggest that eRNAs are likely to exert important functions inmany regulated programs of gene expression in Breast cancer progression.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2013
Accession Number
ADA594737

Entities

People

  • Dimple Notani
  • Michael G. Rosenfeld
  • Richard Schwab

Organizations

  • University of California, San Diego

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Breast Cancer
  • Cells
  • Computer Programming
  • Cytoskeleton
  • Demographic Cohorts
  • Diseases And Disorders
  • Electronic Mail
  • Estrogens
  • Gene Expression
  • Hormones
  • Neoplasms
  • Prostate Cancer
  • Proteins
  • Regulations
  • Tumor Cell Line
  • United States

Fields of Study

  • Biology

Readers

  • Molecular Genetics
  • Prostate Cancer Biology.
  • Women's Health and Cancer Risk Research: African American Women and Pregnancy Outcomes.