Precise spatiotemporal gene regulation is paramount for the establishment and 
maintenance of cell-specific programmes. Although there is evidence that 
chromatin neighbourhoods, formed by the zinc-finger protein CTCF, can sequester 
enhancers and their target genes, there is limited in vivo evidence for CTCF 
demarcating super-enhancers and preventing cross talk between distinct 
regulatory elements. Here, we address these questions in the Wap locus with its 
mammary-specific super-enhancer separated by CTCF sites from widely expressed 
genes. Mutational analysis demonstrates that the Wap super-enhancer controls 
Ramp3, despite three separating CTCF sites. Their deletion in mice results in 
elevated expression of Ramp3 in mammary tissue through augmented 
promoter-enhancer interactions. Deletion of the distal CTCF-binding site results 
in loss of Ramp3 expression in non-mammary tissues. This suggests that CTCF 
sites are porous borders, allowing a super-enhancer to activate a secondary 
target. Likewise, CTCF sites shield a widely expressed gene from suppressive 
influences of a silent locus.