CTCF/cohesin-mediated DNA looping is required for protocadherin α promoter choice.

Abstract

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.

DOI: 10.1073/pnas.1219280110

6 Figures and Tables

05010015020132014201520162017
Citations per Year

382 Citations

Semantic Scholar estimates that this publication has 382 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Guo2012CTCFcohesinmediatedDL, title={CTCF/cohesin-mediated DNA looping is required for protocadherin α promoter choice.}, author={Ya Jie Guo and Kevin Monahan and Haiyang Wu and Jason Gertz and Katherine Elena Varley and Wei Li and Richard Myers and Tom Maniatis and Qiang Wu}, journal={Proceedings of the National Academy of Sciences of the United States of America}, year={2012}, volume={109 51}, pages={21081-6} }