Epigenetic Basis for the Regulation of Estrogen Receptor Alpha Activity in Breast Cancer Cells

Abstract

A key factor involved in breast cancer development and progression is the estrogen receptor alpha (ER). Genome-wide computational studies on ER have identified over 70,000 putative Estrogen Response Elements (EREs) in the human genome. However, a genome-wide functional study using ChIP-Chip, has indicated that less than 1/10 of all putative ER binding sites are recognized by the receptor following estrogen stimulation in breast cancer cells. Through genome-wide positional analyses, we demonstrate that ER recruitment is dependent on a specific epigenetic signature characterized by mono and dimethylation of lysine 4 on histone 3 (H3K4me1/me2). Furthermore the pioneer factor FoxA1 translates this epigenetic signature into changes in chromatin structure in a cell type-specific manner for transcription factors, such as ER. Hence, this allows for the establishment of lineage-specific transcriptional enhancers and programs.

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Document Details

Document Type
Technical Report
Publication Date
Apr 01, 2009
Accession Number
ADA514227

Entities

People

  • Mathieu Lupien

Organizations

  • Dana–Farber Cancer Institute

Tags

DTIC Thesaurus Topics

  • Androgen Receptors
  • Breast Cancer
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Chromosomes
  • Computational Biology
  • Epithelial Cells
  • Gene Expression
  • Genetics
  • Health Services
  • Human Genome
  • Neoplasms
  • Oncology
  • Proteins
  • Stem Cells
  • Transcription Factors

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics
  • Molecular and genetic basis of cancer.