CBFA2T3-ZNF652 corepressor complex regulates transcription of the E-box gene HEB
Date
2008
Authors
Kumar, R.
Cheney, K.
McKirdy, R.
Neilsen, P.
Schulz, R.
Lee, J.
Cohen, J.
Booker, G.
Callen, D.
Editors
Advisors
Journal Title
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Type:
Journal article
Citation
Journal of Biological Chemistry, 2008; 283(27):19026-19038
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
Conference Name
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.
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Copyright © 2008 by the American Society for Biochemistry and Molecular Biology.