Epigenetic Basis for the Regulation of Estrogen Receptor Alpha Activity in Breast Cancer Cells
Annual summary rept. 1 Apr 2008-31 Mar 2009
DANA-FARBER CANCER INST BOSTON MA
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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.
- Medicine and Medical Research