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) : Lupien, Mathieu


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a514227.pdf


Report Date : Apr 2009


Pagination or Media Count : 47


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.


Descriptors :   *RECEPTOR SITES(PHYSIOLOGY) , *BREAST CANCER , *ESTROGENS , *GENOME , CHROMATIN , SENSE ORGANS , RESPONSE(BIOLOGY) , HUMANS


Subject Categories : Biochemistry
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE