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

Julia K. Pagan, Jeremy Arnold, Kim J. Hanchard, Raman Kumar, Tiziana Bruno, Mathew J K Jones, Derek J. Richard, Alistair Forrest, Amanda Spurdle, Eric Verdin, Merlin Crossley, Maurizio Fanciulli, Georgia Chenevix-Trench, David B. Young, Kum Kum Khanna

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)15248-15257
Number of pages10
JournalJournal of Biological Chemistry
Volume282
Issue number20
DOIs
Publication statusPublished - May 18 2007

ASJC Scopus subject areas

  • Biochemistry

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