Immune mediators regulate CFTR expression through a bifunctional airway-selective enhancer.

ABSTRACT: An airway-selective DNase-hypersensitive site (DHS) at kb -35 (DHS-35kb) 5' to the cystic fibrosis transmembrane conductance regulator (CFTR) gene is evident in many lung cell lines and primary human tracheal epithelial cells but is absent from intestinal epithelia. The DHS-35kb contains an element with enhancer activity in 16HBE14o- airway epithelial cells and is enriched for monomethylated H3K4 histones (H3K4me1). We now define a 350-bp region within DHS-35kb which has full enhancer activity and binds interferon regulatory factor 1 (IRF1) and nuclear factor Y (NF-Y) in vitro and in vivo. Small interfering RNA (siRNA)-mediated depletion of IRF1 or overexpression of IRF2, an antagonist of IRF1, reduces CFTR expression in 16HBE14o- cells. NF-Y is critical for maintenance of H3K4me1 enrichme

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC3719672 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature