The cystic fibrosis transmembrane conductance regulator (CFTR) gene lies within 
a topologically associated domain (TAD) in which multiple cis-regulatory 
elements (CREs) and transcription factors (TFs) regulate its cell-specific 
expression. The CREs are recruited to the gene promoter by a looping mechanism 
that depends upon both architectural proteins and specific TFs. An siRNA screen 
to identify TFs coordinating CFTR expression in airway epithelial cells 
suggested an activating role for BTB domain and CNC homolog 1 (BACH1). BACH1 is 
a ubiquitous master regulator of the cellular response to oxidative stress. 
Here, we show that BACH1 may have a dual effect on CFTR expression by direct 
occupancy of CREs at physiological oxygen (∼8%), while indirectly modulating 
expression under conditions of oxidative stress. Hence BACH1, can activate or 
repress the same gene, to fine tune expression in response to environmental cues 
such as cell stress. Furthermore, our 4C-seq data suggest that BACH1 can also 
directly regulate CFTR gene expression by modulating locus architecture through 
occupancy at known enhancers and structural elements, and depletion of BACH1 
alters the higher order chromatin structure.