Abstract
Recent reports have indicated the participation of tight junction (TJ) proteins in the regulation of gene expression and cell proliferation. Here, we have studied the role of zona occludens (ZO)-2, a TJ peripheral protein, in the regulation of cyclin D1 transcription. We found that ZO-2 down-regulates cyclin D1 transcription in a dose-dependent manner. To understand how ZO-2 represses cyclin D1 promoter activity, we used deletion analyses and found that ZO-2 negatively regulates cyclin D1 transcription via an E box and that it diminishes cell proliferation. Because ZO-2 does not associate directly with DNA, electrophoretic mobility shift assay and chromatin immunoprecipitation (ChIP) assay were used to identify the transcription factors mediating the ZO-2–repressive effect. c-Myc was found to bind the E box present in the cyclin D1 promoter, and the overexpression of c-Myc augmented the inhibition generated by ZO-2 transfection. The presence of ZO-2 and c-Myc in the same complex was further demonstrated by immunoprecipitation. ChIP and reporter gene assays using histone deacetylases (HDACs) inhibitors demonstrated that HDACs are necessary for ZO-2 repression and that HDAC1 is recruited to the E box. We conclude that ZO-2 down-regulates cyclin D1 transcription by interacting with the c-Myc/E box element and by recruiting HDAC1.
Bibliography
Huerta, M., Muñoz, R., Tapia, R., Soto-Reyes, E., RamÃrez, L., Recillas-Targa, F., González-Mariscal, L., & López-Bayghen, E. (2007). Cyclin D1 Is Transcriptionally Down-Regulated by ZO-2 via an E Box and the Transcription Factor c-Myc. Molecular Biology of the Cell, 18(12), 4826â4836.
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Dates
Type | When |
---|---|
Created | 17 years, 11 months ago (Sept. 19, 2007, 9:19 p.m.) |
Deposited | 5 years, 3 months ago (April 26, 2020, 1:22 p.m.) |
Indexed | 3 weeks, 2 days ago (July 30, 2025, 11:16 a.m.) |
Issued | 17 years, 8 months ago (Dec. 1, 2007) |
Published | 17 years, 8 months ago (Dec. 1, 2007) |
Published Print | 17 years, 8 months ago (Dec. 1, 2007) |
@article{Huerta_2007, title={Cyclin D1 Is Transcriptionally Down-Regulated by ZO-2 via an E Box and the Transcription Factor c-Myc}, volume={18}, ISSN={1939-4586}, url={http://dx.doi.org/10.1091/mbc.e07-02-0109}, DOI={10.1091/mbc.e07-02-0109}, number={12}, journal={Molecular Biology of the Cell}, publisher={American Society for Cell Biology (ASCB)}, author={Huerta, Miriam and Muñoz, Rodrigo and Tapia, Rocío and Soto-Reyes, Ernesto and Ramírez, Leticia and Recillas-Targa, Félix and González-Mariscal, Lorenza and López-Bayghen, Esther}, editor={Nusrat, Asma}, year={2007}, month=dec, pages={4826–4836} }