Corepressor SMRT binds the BTB/POZ repressing domain of the LAZ3/BCL6 oncoprotein.
The LAZ3/BCL6 (lymphoma-associated zinc finger 3/B cell lymphomas 6) gene frequently is altered in non-Hodgkin lymphomas. It encodes a sequence-specific DNA binding transcriptional repressor that contains a conserved N-terminal domain, termed BTB/POZ (bric-à-brac tramtrack broad complex/pox viruses and zinc fingers). Using a yeast two-hybrid screen, we show here that the LAZ3/BCL6 BTB/POZ domain interacts with the SMRT (silencing mediator of retinoid and thyroid receptor) protein. SMRT originally was identified as a corepressor of unliganded retinoic acid and thyroid receptors and forms a repressive complex with a mammalian homolog of the yeast transcriptional repressor SIN3 and the HDAC-1 histone deacetylase. Protein binding assays demonstrate that the LAZ3/BCL6 BTB/POZ domain directly interacts with SMRT in vitro. Furthermore, DNA-bound LAZ3/BCL6 recruits SMRT in vivo, and both overexpressed proteins completely colocalize in nuclear dots. Finally, overexpression of SMRT enhances the LAZ3/BCL6-mediated repression. These results define SMRT as a corepressor of LAZ3/BCL6 and suggest that LAZ3/BCL6 and nuclear hormone receptors repress transcription through shared mechanisms involving SMRT recruitment and histone deacetylation.
Dhordain
P
P
U124 Institut National de la Santé et de la Recherche Médicale, Institut de Recherches sur le Cancer de Lille Place de Verdun, F-59045 Lille Cedex France. dhordain@infobiogen.fr
Albagli
O
O
Lin
R J
RJ
Ansieau
S
S
Quief
S
S
Leutz
A
A
Kerckaert
J P
JP
Evans
R M
RM
Leprince
D
D
D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D056985:Nuclear Receptor Co-Repressor 2; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic
C490010:Bcl6 protein, mouse; D004268:DNA-Binding Proteins; C539131:Ncor2 protein, mouse; D056985:Nuclear Receptor Co-Repressor 2; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins; D014157:Transcription Factors