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https://hdl.handle.net/2440/47173
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Type: | Journal article |
Title: | CBFA2T3-ZNF652 corepressor complex regulates transcription of the E-box gene HEB |
Author: | Kumar, R. Cheney, K. McKirdy, R. Neilsen, P. Schulz, R. Lee, J. Cohen, J. Booker, G. Callen, D. |
Citation: | Journal of Biological Chemistry, 2008; 283(27):19026-19038 |
Publisher: | Amer Soc Biochemistry Molecular Biology Inc |
Issue Date: | 2008 |
ISSN: | 0021-9258 1083-351X |
Statement of Responsibility: | 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. |
DOI: | 10.1074/jbc.M709136200 |
Published version: | http://www.jbc.org/cgi/content/abstract/283/27/19026 |
Appears in Collections: | Aurora harvest 6 Molecular and Biomedical Science publications |
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