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A novel corepressor, BCoR-L1, represses transcription through an interaction with CtBP

Pagan, Julia K., Arnold, Jeremy, Hanchard, Kim J., Kumar, Raman, Bruno, Tiziana, Jones, Mathew J. K., Richard, Derek J., Forrest, Alistair, Spurdle, Amanda B., Verdin, Eric, Crossley, Merlin, Fanciulli, Maurizio, Chenevix-Trench, Georgia, Young, David B., & Khanna, Kum Kum (2007) A novel corepressor, BCoR-L1, represses transcription through an interaction with CtBP. Journal of Biological Chemistry, 282(20), pp. 15248-15257.

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Abstract

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.

Impact and interest:

15 citations in Scopus
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15 citations in Web of Science®

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ID Code: 40610
Item Type: Journal Article
Keywords: negative gene regulation, BCL6 repressor protein, BCoR-L1
DOI: 10.1074/jbc.M700246200
ISSN: 0021-9258
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100)
Divisions: Past > QUT Faculties & Divisions > Faculty of Science and Technology
Copyright Owner: Copyright 2007 American Society for Biochemistry and Molecular Biology
Deposited On: 09 Mar 2011 14:09
Last Modified: 01 Mar 2012 00:31

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