Estrogen plays an essential physiologic role in reproduction and a pathologic 
one in breast cancer. The completion of the human genome has allowed the 
identification of the expressed regions of protein-coding genes; however, little 
is known concerning the organization of their cis-regulatory elements. We have 
mapped the association of the estrogen receptor (ER) with the complete 
nonrepetitive sequence of human chromosomes 21 and 22 by combining chromatin 
immunoprecipitation (ChIP) with tiled microarrays. ER binds selectively to a 
limited number of sites, the majority of which are distant from the 
transcription start sites of regulated genes. The unbiased sequence 
interrogation of the genuine chromatin binding sites suggests that direct ER 
binding requires the presence of Forkhead factor binding in close proximity. 
Furthermore, knockdown of FoxA1 expression blocks the association of ER with 
chromatin and estrogen-induced gene expression demonstrating the necessity of 
FoxA1 in mediating an estrogen response in breast cancer cells.