Estrogen receptor action in three dimensions - looping the loop

Vasiliki Theodorou,Jason S Carroll

doi:10.1186/bcr2470

Abstract

Due to advances in genomic technologies, our understanding of estrogen receptor (ER)-mediated transcription in breast cancer cells has evolved significantly in recent years. Genome-wide mapping experiments revealed thousands of ER-binding events, but linking them to the target genes has been an ongoing struggle. A recent paper describes a new technique, called ChIA-PET (chromatin interaction analysis using paired-end tag sequencing), that can directly address these questions. ChIA-PET is an unbiased approach for simultaneously identifying all genome-wide binding events of a transcription factor and those involved in long-range chromatin loops.

Highlights

Estrogen receptor (ER) has been one of the most intensively studied transcription factors, primarily due to its importance in breast cancer
Much effort has been invested in identifying the target genes of ER, mainly by expression arrays in breast cancer cell lines and in human tumour samples [1,2]
This involves combining chromatin immunoprecipitation with microarrays or highthroughput sequencing in order to identify ER contact points within the genome. These genome-wide experiments revealed a number of surprising features about ER biology, the most unexpected one being that ER regulates transcription mostly from distal enhancers. This finding raised the subsequent question: which of the thousands of ER-binding events are the functional ones that regulate expression of the few hundred ER target genes? Fullwood and colleagues [5] have established a method for addressing this question, allowing researchers to assign ERbinding events to transcriptional hubs and target genes

Summary

Introduction

Estrogen receptor (ER) has been one of the most intensively studied transcription factors, primarily due to its importance in breast cancer. Much effort has been invested in identifying the target genes of ER, mainly by expression arrays in breast cancer cell lines and in human tumour samples [1,2]. This finding raised the subsequent question: which of the thousands of ER-binding events are the functional ones that regulate expression of the few hundred ER target genes?

Results

Conclusion