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Interrogating the genome to understand oestrogen-receptor-mediated transcription

Published online by Cambridge University Press:  01 April 2008

Sara C. Dietz
Affiliation:
Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.
Jason S. Carroll*
Affiliation:
Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.
*
*Corresponding author: Jason S. Carroll, Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK. Tel:  + 44 (0)1223 404510; Fax:  + 44 (0)1223 404199; E-mail: jason.carroll@cancer.org.uk

Abstract

Defining transcription mediated by the oestrogen (estrogen) receptor (ER) in breast cancer cell models has been an area of interest for many years. Initial studies focused on promoter regions of putative target genes and revealed significant insight into the basis of ER binding to DNA. More recently, the complexities of ER transcription are starting to become apparent. It is now clear that ER can regulate gene targets from significant distances and that cooperating transcription factors play an integral role in ER activity. It is also clear that the sequence information defining an in vivo ER-binding site is more complicated than initially thought. However, contemporary genomic tools based on chromatin immunoprecipitation (ChIP) – such as ChIP-on-chip and ChIP–sequencing – and gene expression profiling have allowed us to redefine the underlying properties of ER biology on a genomic scale. The advances in technology that have permitted a better understanding of how and where ER can bind to DNA are discussed in this review. The possible clinical implications of these findings for understanding the role of oestrogen in breast cancer are also briefly considered.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2008

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References

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Further reading, resources and contacts

The NURSA website provides the most extensive information on nuclear receptors and their transcriptional properties:

Baek, S.H. and Rosenfeld, M.G. (2004) Nuclear receptor coregulators: their modification codes and regulatory mechanism by translocation. Biochem Biophys Res Commun 319, 707-714CrossRefGoogle ScholarPubMed
Buck, M.J. and Lieb, J.D. (2004) ChIP-on-chip: considerations for the design, analysis, and application of genome-wide chromatin immunoprecipitation experiments. Genomics 83, 349-360CrossRefGoogle ScholarPubMed
Hudson, M.E. and Snyder, M. (2006) High-throughput methods of regulatory element discovery. Biotechniques 41, 673, 675, 677 passimCrossRefGoogle ScholarPubMed
Baek, S.H. and Rosenfeld, M.G. (2004) Nuclear receptor coregulators: their modification codes and regulatory mechanism by translocation. Biochem Biophys Res Commun 319, 707-714CrossRefGoogle ScholarPubMed
Buck, M.J. and Lieb, J.D. (2004) ChIP-on-chip: considerations for the design, analysis, and application of genome-wide chromatin immunoprecipitation experiments. Genomics 83, 349-360CrossRefGoogle ScholarPubMed
Hudson, M.E. and Snyder, M. (2006) High-throughput methods of regulatory element discovery. Biotechniques 41, 673, 675, 677 passimCrossRefGoogle ScholarPubMed