The closely linked human protocadherin (Pcdh) α, β, and γ gene clusters encode 
53 distinct protein isoforms, which are expressed in a combinatorial manner to 
generate enormous diversity on the surface of individual neurons. This diversity 
is a consequence of stochastic promoter choice and alternative pre-mRNA 
processing. Here, we show that Pcdhα promoter choice is achieved by DNA looping 
between two downstream transcriptional enhancers and individual promoters 
driving the expression of alternate Pcdhα isoforms. In addition, we show that 
this DNA looping requires specific binding of the CTCF/cohesin complex to two 
symmetrically aligned binding sites in both the transcriptionally active 
promoters and in one of the enhancers. These findings have important 
implications regarding enhancer/promoter interactions in the generation of 
complex Pcdh cell surface codes for the establishment of neuronal identity and 
self-avoidance in individual neurons.