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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
Statement of
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
Breast Neoplasms
Cell Transformation, Neoplastic
Multiprotein Complexes
DNA-Binding Proteins
Proto-Oncogene Proteins
Tumor Suppressor Proteins
Transcription Factors
Repressor Proteins
Transcription, Genetic
Gene Expression Regulation, Neoplastic
Response Elements
Protein Structure, Tertiary
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:
Appears in Collections:Aurora harvest 6
Molecular and Biomedical Science publications

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