CTCF/cohesin-mediated DNA Looping is Required for Protocadherin α Promoter Choice

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2012 Dec 4

PMID 23204437

Citations 136

Authors

Ya Guo

Kevin Monahan

Haiyang Wu

Jason Gertz

Katherine E Varley

Wei Li

Richard M Myers

Tom Maniatis

Qiang Wu

Affiliations

Soon will be listed here.

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.

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