Chromatin immunoprecipitation followed by massively parallel sequencing 
(ChIP-seq) is rapidly enabling the comprehensive characterization of genome-wide 
transcription factor-binding sites, thus defining the cistrome (cis-acting DNA 
targets of a trans-acting factor). Estrogen receptor (ER) ChIP-seq studies have 
been performed mainly in cell lines, but Ross-Innes and colleagues have now 
completed the first such study in clinical breast cancer samples. The study 
aimed at determining the dynamics of ER binding and differences between more and 
less aggressive primary breast tumors and metastases. The authors found that ER 
bound to DNA in both aggressive and drug-resistant tumors but to different sites 
and with different affinities. Given previous findings from cell lines, FoxA1 
appears to play a critical role in this reprogramming of ER binding.