Kumar, R.Cheney, K.McKirdy, R.Neilsen, P.Schulz, R.Lee, J.Cohen, J.Booker, G.Callen, D.2008-08-052008-08-052008Journal of Biological Chemistry, 2008; 283(27):19026-190380021-92581083-351Xhttp://hdl.handle.net/2440/47173Copyright © 2008 by the American Society for Biochemistry and Molecular Biology.Transcriptional repression plays a critical role in development and homeostasis. The ETO family represents a group of highly conserved and ubiquitously expressed transcriptional regulatory proteins that are components of a diverse range of multiprotein repressor complexes. ETO proteins function as transcriptional repressors by interacting with a number of transcription factors that bind to their cognate consensus DNA binding sequences within the promoters of target genes. We previously reported that the classical C2H2 zinc finger DNA-binding protein, ZNF652, specifically and functionally interacts with the ETO protein CBFA2T3 and has a role in the suppression of breast oncogenesis. Here we report the identification and validation of the ZNF652 consensus DNA binding sequence. Our results show that the E-box gene HEB is a direct target of CBFA2T3-ZNF652-mediated transcriptional repression. The CBFA2T3-ZNF652 complex regulates HEB expression by binding to a single ZNF652 response element located within the promoter sequence of HEB. This study also shows that the NHR3 and NHR4 domains of CBFA2T3 interact with a conserved proline-rich region located within the C terminus of ZNF652. Our results, together with previous reports, indicate that HEB has a complex relationship with CBFA2T3; CBFA2T3 interacts with ZNF652 to repress HEB expression, and in addition CBFA2T3 interacts with the HEB protein to inhibit its activator function. These findings suggest that CBFA2T3-ZNF652-mediated HEB regulation may play an important role in hematopoiesis and myogenesis.enJurkat CellsCHO CellsAnimalsHumansCricetulusBreast NeoplasmsCell Transformation, NeoplasticMultiprotein ComplexesDNA-Binding ProteinsProto-Oncogene ProteinsTumor Suppressor ProteinsPhosphoproteinsTranscription FactorsRepressor ProteinsTranscription, GeneticGene Expression Regulation, NeoplasticResponse ElementsProtein Structure, TertiaryFemaleCricetinaeBasic Helix-Loop-Helix Transcription FactorsRUNX1 Translocation Partner 1 ProteinJournal article002008120010.1074/jbc.M7091362000002571656000582-s2.0-4964910675242990Booker, G. [0000-0001-7207-4699]Callen, D. [0000-0002-6189-9991]