PUBLICATION
Regulation of protocadherin gene expression by multiple neuron-restrictive silencer elements scattered in the gene cluster
- Authors
- Tan, Y.P., Li, S., Jiang, X.J., Loh, W., Foo, Y.K., Loh, C.B., Xu, Q., Yuen, W.H., Jones, M., Fu, J., Venkatesh, B., and Yu, W.P.
- ID
- ZDB-PUB-100420-22
- Date
- 2010
- Source
- Nucleic acids research 38(15): 4985-4997 (Journal)
- Registered Authors
- Venkatesh, Byrappa
- Keywords
- none
- MeSH Terms
-
- Animals
- Cadherins/genetics*
- Cell Line
- Gene Silencing*
- Humans
- Mice
- Multigene Family*
- Neurons/metabolism*
- Promoter Regions, Genetic
- Silencer Elements, Transcriptional*
- Takifugu/genetics
- Xenopus laevis
- Zebrafish/genetics
- PubMed
- 20385576 Full text @ Nucleic Acids Res.
Citation
Tan, Y.P., Li, S., Jiang, X.J., Loh, W., Foo, Y.K., Loh, C.B., Xu, Q., Yuen, W.H., Jones, M., Fu, J., Venkatesh, B., and Yu, W.P. (2010) Regulation of protocadherin gene expression by multiple neuron-restrictive silencer elements scattered in the gene cluster. Nucleic acids research. 38(15):4985-4997.
Abstract
The clustered protocadherins are a subfamily of neuronal cell adhesion molecules that play an important role in development of the nervous systems in vertebrates. The clustered protocadherin genes exhibit complex expression patterns in the central nervous system. In this study, we have investigated the molecular mechanism underlying neuronal expression of protocadherin genes using the protocadherin gene cluster in fugu as a model. By in silico prediction, we identified multiple neuron-restrictive silencer elements (NRSEs) scattered in the fugu protocadherin cluster and demonstrated that these elements bind specifically to NRSF/REST in vitro and in vivo. By using a transgenic Xenopus approach, we show that these NRSEs regulate neuronal specificity of protocadherin promoters by suppressing their activity in non-neuronal tissues. We provide evidence that protocadherin genes that do not contain an NRSE in their 5' intergenic region are regulated by NRSEs in the regulatory region of their neighboring genes. We also show that protocadherin clusters in other vertebrates such as elephant shark, zebrafish, coelacanth, lizard, mouse and human, contain different sets of multiple NRSEs. Taken together, our data suggest that the neuronal specificity of protocadherin cluster genes in vertebrates is regulated by the NRSE-NRSF/REST system.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping