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

作者: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*
来源:JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282(20): 15248-15257.
DOI:10.1074/jbc.M700246200

摘要

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.