Coordinated histone modifications mediated by a CtBP co-repressor complex

Yujiang Shi, Jun-ichi Sawada, Guangchao Sui, El Bachir Affar, Johnathan R. Whetstine, Fei Lan, Hidesato Ogawa, Margaret Po-Shan Luke, Yoshihiro Nakatani and Yang Shi ()
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Yujiang Shi: Harvard Medical School
Jun-ichi Sawada: Dana-Farber Cancer Institute
Guangchao Sui: Harvard Medical School
El Bachir Affar: Harvard Medical School
Johnathan R. Whetstine: Harvard Medical School
Fei Lan: Harvard Medical School
Hidesato Ogawa: Dana-Farber Cancer Institute
Margaret Po-Shan Luke: Harvard Medical School
Yoshihiro Nakatani: Dana-Farber Cancer Institute
Yang Shi: Harvard Medical School

Nature, 2003, vol. 422, issue 6933, 735-738

Abstract: Abstract The transcriptional co-repressor CtBP (C-terminal binding protein) is implicated in tumorigenesis because it is targeted by the adenovirus E1A protein during oncogenic transformation1. Genetic studies have also identified a crucial function for CtBP in animal development2. CtBP is recruited to DNA by transcription factors that contain a PXDLS motif3,4, but the detailed molecular events after the recruitment of CtBP to DNA and the mechanism of CtBP function in tumorigenesis are largely unknown. Here we report the identification of a CtBP complex that contains the essential components for both gene targeting and coordinated histone modifications, allowing for the effective repression of genes targeted by CtBP. Inhibiting the expression of CtBP and its associated histone-modifying activities by RNA-mediated interference resulted in alterations of histone modifications at the promoter of the tumour invasion suppressor gene E-cadherin and increased promoter activity in a reporter assay. These findings identify a molecular mechanism by which CtBP mediates transcriptional repression and provide insight into CtBP participation in oncogenesis.

Date: 2003
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DOI: 10.1038/nature01550

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