COREPRESSOR SMRT BINDS THE BTB POZ REPRESSING DOMAIN OF THE LAZ3/BCL6ONCOPROTEIN/

The LAZ3/BCL6 (lymphoma-associated zinc finger 3/B cell lymphomas 6) g ene frequently is altered in non-Hodgkin lymphomas. It encodes a seque nce-specific DNA binding transcriptional repressor that-contains a con served N-terminal domain, termed BTB/POZ (bric-a-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 SM RT (silencing mediator of retinoid and thyroid receptor) protein. SMRT originally was identified as a corepressor of unliganded retinoic aci d and thyroid receptors and forms a repressive complex with a mammalia n homolog of the yeast transcriptional repressor SIN3 and the HDAC-1 h istone deacetylase. Protein binding assays demonstrate that the LAZ3/B CL6 BTB/POZ domain directly interacts with SMRT in vitro. Furthermore, DNA-bound LAZ3/BCL6 recruits SMRT in vivo, and both overexpressed pro teins completely colocalize in nuclear dots, Finally, overexpression o f SMRT enhances the LAZ3/BCL6-mediated repression. These results defin e SMRT as a corepressor of LAZ3/BCL6 and suggest that LAZ3/BCL6 and nu clear hormone receptors repress transcription through shared mechanism s involving SMRT recruitment and histone deacetylation.