Regulatory elements required for the activation and repression of the protocadherin-alpha gene cluster.
paper
Cited
Public
Unavailable
- Authors
- Kehayova, Polina; Monahan, Kevin; Chen, Weisheng; Maniatis, Tom
- Year
- 2011
- Journal
- Proceedings of the National Academy of Sciences of the United States of America
- PMID
- 21949399
- DOI
- 10.1073/pnas.1114357108
- PMCID
- PMC3193253
The mouse protocadherin (Pcdh) -Ξ±, -Ξ², and -Ξ³ gene clusters encode more than 50 protein isoforms, the combinatorial expression of which generates vast single-cell diversity in the brain. At present, the mechanisms by which this diversity is expressed are not understood. Here we show that two transcriptional enhancer elements, HS5-1 and HS7, play a critical role in PcdhΞ± gene expression in mice. We show that the HS5-1 element functions as an enhancer in neurons and a silencer in nonneuronal cells. The enhancer activity correlates with the binding of zinc finger DNA binding protein CTCF to the target promoters, and the silencer activity requires the binding of the REST/NRSF repressor complex in nonneuronal cells. Thus, the HS5-1 element functions as a neuron-specific enhancer and nonneuronal cell repressor. In contrast, the HS7 element functions as a PcdhΞ± cluster-wide transcription enhancer element. These studies reveal a complex organization of regulatory elements required for generating single cell Pcdh diversity.
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