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 journalArticle

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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.

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

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Co-Repressor Proteins
Cadherins
Transcription
Repressor Proteins
Histone Deacetylases
RNA Interference
Gene expression
Assays
Binding Sites
RNA
Genes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Pagan, J. K., Arnold, J., Hanchard, K. J., Kumar, R., Bruno, T., Jones, M. J. K., ... Khanna, K. K. (2007). A novel corepressor, BCoR-L1, represses transcription through an interaction with CtBP. Journal of Biological Chemistry, 282(20), 15248-15257. https://doi.org/10.1074/jbc.M700246200

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; Verdin, Eric; Crossley, Merlin; Fanciulli, Maurizio; Chenevix-Trench, Georgia; Young, David B.; Khanna, Kum Kum.

In: Journal of Biological Chemistry, Vol. 282, No. 20, 18.05.2007, p. 15248-15257.

Research output: Contribution to journalArticle

Pagan, JK, Arnold, J, Hanchard, KJ, Kumar, R, Bruno, T, Jones, MJK, Richard, DJ, Forrest, A, Spurdle, A, Verdin, E, Crossley, M, Fanciulli, M, Chenevix-Trench, G, Young, DB & Khanna, KK 2007, 'A novel corepressor, BCoR-L1, represses transcription through an interaction with CtBP', Journal of Biological Chemistry, vol. 282, no. 20, pp. 15248-15257. https://doi.org/10.1074/jbc.M700246200
Pagan JK, Arnold J, Hanchard KJ, Kumar R, Bruno T, Jones MJK et al. A novel corepressor, BCoR-L1, represses transcription through an interaction with CtBP. Journal of Biological Chemistry. 2007 May 18;282(20):15248-15257. https://doi.org/10.1074/jbc.M700246200
Pagan, Julia K. ; Arnold, Jeremy ; Hanchard, Kim J. ; Kumar, Raman ; Bruno, Tiziana ; Jones, Mathew J K ; Richard, Derek J. ; Forrest, Alistair ; Spurdle, Amanda ; Verdin, Eric ; Crossley, Merlin ; Fanciulli, Maurizio ; Chenevix-Trench, Georgia ; Young, David B. ; Khanna, Kum Kum. / A novel corepressor, BCoR-L1, represses transcription through an interaction with CtBP. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 20. pp. 15248-15257.
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