A novel corepressor, BCoR-L1, represses transcription through an interaction with CtBP.
Corepressors play a crucial role in negative gene regulation and are defective in several diseases. BCoR is a corepressor for the BCL6 repressor protein. Here we describe and functionally characterize BCoR-L1, a homolog of BCoR. When tethered to a heterologous promoter, BCoR-L1 is capable of strong repression. Like other corepressors, ... BCoR-L1 associates with histone deacetylase (HDAC) activity. Specifically, BCoR-L1 coprecipitates with the Class II HDACs, HDAC4, HDAC5, and HDAC7, suggesting that they are involved in its role as a transcriptional repressor. BCoR-L1 also interacts with the CtBP corepressor through a CtBP-interacting motif in its amino terminus. Abrogation of the CtBP binding site within BCoR-L1 partially relieves BCoR-L1-mediated transcriptional repression. Furthermore, BCoR-L1 is located on the E-cadherin promoter, a known CtBP-regulated promoter, and represses the E-cadherin promoter activity in a reporter assay. The inhibition of BCoR-L1 expression by RNA-mediated interference results in derepression of E-cadherin in cells that do not normally express E-cadherin, indicating that BCoR-L1 contributes to the repression of an authentic endogenous CtBP target.
Mesh Terms:
Alcohol Oxidoreductases, Amino Acid Motifs, Animals, Binding Sites, Cadherins, Cell Line, DNA-Binding Proteins, Gene Expression Regulation, Histone Deacetylases, Humans, Mice, Multiprotein Complexes, Promoter Regions, Genetic, Protein Binding, RNA Interference, Repressor Proteins
Alcohol Oxidoreductases, Amino Acid Motifs, Animals, Binding Sites, Cadherins, Cell Line, DNA-Binding Proteins, Gene Expression Regulation, Histone Deacetylases, Humans, Mice, Multiprotein Complexes, Promoter Regions, Genetic, Protein Binding, RNA Interference, Repressor Proteins
J. Biol. Chem.
Date: May. 18, 2007
PubMed ID: 17379597
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