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.
Pagan
Julia K
JK
Queensland Institute of Medical Research, 300 Herston Road, Herston 4029, Queensland, Australia.
Arnold
Jeremy
J
Hanchard
Kim J
KJ
Kumar
Raman
R
Bruno
Tiziana
T
Jones
Mathew J K
MJ
Richard
Derek J
DJ
Forrest
Alistair
A
Spurdle
Amanda
A
Verdin
Eric
E
Crossley
Merlin
M
Fanciulli
Maurizio
M
Chenevix-Trench
Georgia
G
Young
David B
DB
Khanna
Kum Kum
KK
D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology; D011485:Protein Binding / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
C084103:BCL6 protein, human; C521111:BCORL1 protein, human; C490010:Bcl6 protein, mouse; D015820:Cadherins; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein; D006655:Histone Deacetylases