Accession Number:

ADA514227

Title:

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

Descriptive Note:

Annual summary rept. 1 Apr 2008-31 Mar 2009

Corporate Author:

DANA-FARBER CANCER INST BOSTON MA

Personal Author(s):

Report Date:

2009-04-01

Pagination or Media Count:

47.0

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 110 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 H3K4me1me2. 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.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE