Interrogating the genome to understand oestrogen-receptor-mediated transcription

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.