TY - JOUR
T1 - Coordinated histone modifications mediated by a CtBP co-repressor complex
AU - Shi, Yujiang
AU - Sawada, Jun Ichi
AU - Sui, Guangchao
AU - Affar, El Bachir
AU - Whetstine, Johnathan R.
AU - Lan, Fei
AU - Ogawa, Hidesato
AU - Luke, Margaret Po Shan
AU - Nakatani, Yoshihiro
AU - Shi, Yang
PY - 2003/4/17
Y1 - 2003/4/17
N2 - The transcriptional co-repressor CtBP (C-terminal binding protein) is implicated in tumorigenesis because it is targeted by the adenovirus E1A protein during oncogenic transformation. Genetic studies have also identified a crucial function for CtBP in animal development. CtBP is recruited to DNA by transcription factors that contain a PXDLS motif, 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.
AB - The transcriptional co-repressor CtBP (C-terminal binding protein) is implicated in tumorigenesis because it is targeted by the adenovirus E1A protein during oncogenic transformation. Genetic studies have also identified a crucial function for CtBP in animal development. CtBP is recruited to DNA by transcription factors that contain a PXDLS motif, 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.
KW - Alcohol Oxidoreductases
KW - Cadherins/genetics
KW - Chromatin/genetics
KW - DNA-Binding Proteins/genetics
KW - Gene Expression Regulation
KW - Histone Deacetylases/metabolism
KW - Histone Methyltransferases
KW - Histone-Lysine N-Methyltransferase
KW - Histones/metabolism
KW - Humans
KW - Macromolecular Substances
KW - Methyltransferases/metabolism
KW - Phosphoproteins/genetics
KW - Promoter Regions, Genetic/genetics
KW - Protein Methyltransferases
KW - RNA Interference
KW - Repressor Proteins/genetics
UR - http://www.scopus.com/inward/record.url?scp=0242669199&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:000182272300045&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1038/nature01550
DO - 10.1038/nature01550
M3 - Article
C2 - 12700765
SN - 0028-0836
VL - 422
SP - 735
EP - 738
JO - Nature
JF - Nature
IS - 6933
ER -