Transcription activation by estrogen receptor (ER) is rapid and dynamic. How the 
prompt and precise ER response is established and maintained is still not fully 
understood. Here, we report that two boundary elements surrounding the well 
defined ERalpha target TFF1 locus are occupied by the CCCTC-binding factor 
(CTCF). These elements are separated by 40 kb but cluster in the nuclear space 
depending on CTCF but independent of estrogen and transcription. In contrast, in 
estrogen non-responsive breast cancer cells, the spatial proximity of these two 
elements is lost and the entire locus instead displays a polycomb repressive 
complex 2-controlled heterochromatin characteristic. We showed that CTCF acts 
upstream of the "pioneer" factor FOXA1 in determining the genomic response to 
estrogen. We propose that the CTCF-bound boundary elements demarcate active 
versus inactive regions, building a framework of adjacent chromosome territory 
that predisposes ERalpha-regulated transcription.