Please use this identifier to cite or link to this item:
http://hdl.handle.net/11375/22452
Title: | The Catenin p120^ctn Regulates Kaiso-Mediated Transcriptional Repression |
Authors: | Spring, Christopher |
Advisor: | Daniel, Juliet |
Department: | Biology |
Keywords: | Catenin;Transcriptional Repression |
Publication Date: | Sep-2003 |
Abstract: | Kaiso is a POZ-ZF transcription factor initially identified as an interaction partner for the cell adhesion co-factor p120^ctn. Kaiso-DNA binding is inhibited by p120^ctn, implicating p120^ctn in the regulation of Kaiso transcriptional activity. In this study, Kaiso repressed transcription of a luciferase reporter carrying four copies of the sequence-specific Kaiso-binding site (4xKBS) in artificial promoter assays. Mutation of the 4xKBS which is known to disrupt Kaiso-DNA binding also abrogated Kaiso-mediated transcriptional repression. Moreover, p120^ctn inhibited Kaiso-mediated transcriptional repression via the 4xKBS, yet neither the p120^ctn deletion mutant ΔR3-ll (lacking the Kaiso binding site) or p120^ctn NLS mutant (which cannot enter the nucleus) inhibited transcriptional repression. Furthermore, in NIH 3T3 cells (which do not demonstrate a Kaiso-pl20ctn interaction), pl20ctn failed to inhibit transcriptional repression. Many POZZF transcriptional repressors recruit an HDAC complex via their POZ domain to repress transcription. To investigate the mechanism of Kaiso-mediated transcriptional repression, the POZ domain of Kaiso was deleted, which abrogated transcriptional repression. Kaiso immunoprecipitates contained HDAC activity, and the HDAC co-repressor Sin3A co-immunoprecipitated with Kaiso, implying that Kaiso recruits Sin3A to repress transcription in an HDAC-dependent manner. Lastly, Kaiso repressed transcription via a human 𝑚𝑎𝑡𝑟𝑖𝑙𝑦𝑠𝑖𝑛 promoter fragment. This suggests that the KBS element is functionally relevant and implicates 𝑚𝑎𝑡𝑟𝑖𝑙𝑦𝑠𝑖𝑛 as a Kaiso target-gene. Collectively, these data establish Kaiso as a sequence-specific, HDAC-dependent transcriptional repressor that is regulated by the adhesion co-factor p120^ctn. |
URI: | http://hdl.handle.net/11375/22452 |
Appears in Collections: | Digitized Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
spring_christopher_m_masters.pdf.pdf | 11.83 MB | Adobe PDF | View/Open |
Items in MacSphere are protected by copyright, with all rights reserved, unless otherwise indicated.