CBFA2T3-ZNF652 corepressor complex regulates transcription of the E-box gene HEB

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dc.contributor.authorKumar, R.
dc.contributor.authorCheney, K.
dc.contributor.authorMcKirdy, R.
dc.contributor.authorNeilsen, P.
dc.contributor.authorSchulz, R.
dc.contributor.authorLee, J.
dc.contributor.authorCohen, J.
dc.contributor.authorBooker, G.
dc.contributor.authorCallen, D.
dc.date.issued2008
dc.descriptionCopyright © 2008 by the American Society for Biochemistry and Molecular Biology.
dc.description.abstractTranscriptional 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.
dc.description.statementofresponsibilityRaman Kumar, Kelly M. Cheney, Ross McKirdy, Paul M. Neilsen, Renèe B. Schulz, Jaclyn Lee, Juliane Cohen, Grant W. Booker, and David F. Callen
dc.identifier.citationJournal of Biological Chemistry, 2008; 283(27):19026-19038
dc.identifier.doi10.1074/jbc.M709136200
dc.identifier.issn0021-9258
dc.identifier.issn1083-351X
dc.identifier.orcidBooker, G. [0000-0001-7207-4699]
dc.identifier.orcidCallen, D. [0000-0002-6189-9991]
dc.identifier.urihttp://hdl.handle.net/2440/47173
dc.language.isoen
dc.publisherAmer Soc Biochemistry Molecular Biology Inc
dc.source.urihttp://www.jbc.org/cgi/content/abstract/283/27/19026
dc.subjectJurkat Cells
dc.subjectCHO Cells
dc.subjectAnimals
dc.subjectHumans
dc.subjectCricetulus
dc.subjectBreast Neoplasms
dc.subjectCell Transformation, Neoplastic
dc.subjectMultiprotein Complexes
dc.subjectDNA-Binding Proteins
dc.subjectProto-Oncogene Proteins
dc.subjectTumor Suppressor Proteins
dc.subjectPhosphoproteins
dc.subjectTranscription Factors
dc.subjectRepressor Proteins
dc.subjectTranscription, Genetic
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectResponse Elements
dc.subjectProtein Structure, Tertiary
dc.subjectFemale
dc.subjectCricetinae
dc.subjectBasic Helix-Loop-Helix Transcription Factors
dc.subjectRUNX1 Translocation Partner 1 Protein
dc.titleCBFA2T3-ZNF652 corepressor complex regulates transcription of the E-box gene HEB
dc.typeJournal article
pubs.publication-statusPublished

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