Genome-wide mapping of estrogen: receptor binding sites and activity

Published on March 30, 2009 Updated on September 18, 2020   51 min

Other Talks in the Therapeutic Area: Gynaecology & Obstetrics

0:00
My name is Jason Carroll. I'm a group leader at Cancer Research UK, at the Cambridge Research Institute at the University of Cambridge. What I'm going to talk about today is some work that's come from ChIP-on-chip experiments over the last couple of years, where we've mapped oestrogen receptor binding sites on a genome-wide level, and we've been mining these binding sites to learn about underlying properties and features of oestrogen receptor transcription in breast cancer cells.
0:27
We are interested in the role of the oestrogen receptor in breast cancer. We know from the genomic revolution about seven or eight years ago that when researchers performed gene expression profiling in primary breast cancers and looked for patterns within the gene expression profiles, they found that primary breast cancers could be subcategorised into various subtypes. This included basal tumours that were driven by ERBB2, but by far the largest category of tumours were those that were called 'luminal tumours'. These were tumours that expressed the oestrogen receptor, and tended to express oestrogen receptor target genes. This shows the large percentage of breast cancers that are represented by luminal or ER-positive breast cancers (n.b., the abbreviation ER uses the US spelling 'estrogen').
1:11
On a molecular level, this is probably the most simplified version of how oestrogen and oestrogen receptor can generate gene transcription events, that can culminate in cell division in breast cancer cells. We know that oestrogen is a steroid. It can diffuse into breast cancer cells and it binds to an intracellular protein, namely oestrogen receptor. Oestrogen receptor can dimerize and these homodimers can bind to the promoters of target genes. These target genes are subsequently transcribed by the transcription machinery, and the gene transcription events that culminate from these pathways represent the gene expression profiles that you see in luminal or ER-positive breast cancers. With the knowledge that oestrogen receptor bound to promoters of specific target genes, we could use technology and technological advances (such as chromatin immunoprecipitations) to map oestrogen receptor binding sites, and to guess about particular co-factors or proteins that might be on the promoters of these target genes.
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Genome-wide mapping of estrogen: receptor binding sites and activity

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