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|Title:||CBFA2T3-ZNF652 corepressor complex regulates transcription of the E-box gene HEB|
|Citation:||Journal of Biological Chemistry, 2008; 283(27):19026-19038|
|Publisher:||Amer Soc Biochemistry Molecular Biology Inc|
|Raman Kumar, Kelly M. Cheney, Ross McKirdy, Paul M. Neilsen, Renèe B. Schulz, Jaclyn Lee, Juliane Cohen, Grant W. Booker, and David F. Callen|
|Abstract:||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.|
|Keywords:||Jurkat Cells; CHO Cells; Animals; Humans; Cricetulus; Breast Neoplasms; Cell Transformation, Neoplastic; Multiprotein Complexes; DNA-Binding Proteins; Proto-Oncogene Proteins; Tumor Suppressor Proteins; Phosphoproteins; Transcription Factors; Repressor Proteins; Transcription, Genetic; Gene Expression Regulation, Neoplastic; Response Elements; Protein Structure, Tertiary; Female; Cricetinae; Basic Helix-Loop-Helix Transcription Factors; RUNX1 Translocation Partner 1 Protein|
|Description:||Copyright © 2008 by the American Society for Biochemistry and Molecular Biology.|
|Appears in Collections:||Molecular and Biomedical Science publications|
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