The Sp1-like family of transcription factors is emerging as an integral part of the cellular machinery involved in the control of gene expression. Members of this family of proteins contain three highly homologous C-terminal zinc-finger motifs that bind GC-rich sequences found in the promoters of a diverse number of genes, such as the basic transcription element (BTE) in the promoter of the carcinogen-metabolizing cytochrome P4501A1 (CYP1A1) gene. In the present study, we report the molecular and functional characterization of BTE-binding protein (BTEB) 4, a novel ubiquitously expressed member of the Sp1-like proteins family. This protein represents a new homologue of BTEB1, originally described as a regulator of the BTE site in the CYP1A1 gene promoter. Similarly to the recently described BTEB3, we demonstrate that the N-terminal region of BTEB4 directly represses transcription and binds the co-repressor mSin3A. In addition, we show that the C-terminal zinc-finger domain of BTEB4 binds specifically the BTE site of the CYP1A1 promoter, similar to BTEB1 and BTEB3. Also, we show that both BTEB3 and BTEB4 repress the CYP1A1 gene promoter via the BTE site in HepG2 and BxPC3 cells. Thus the identification of this protein expands the repertoire of BTEB-like members of the Sp1-like protein family involved in transcriptional repression. Furthermore, our results demonstrate that the BTEB subfamily can repress the CYP1A1 gene promoter via the BTE site.
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September 2002
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Research Article|
September 15 2002
Functional analysis of basic transcription element (BTE)-binding protein (BTEB) 3 and BTEB4, a novel Sp1-like protein, reveals a subfamily of transcriptional repressors for the BTE site of the cytochrome P4501A1 gene promoter
Joanna A. KACZYNSKI;
Joanna A. KACZYNSKI
1
∗Gastroenterology Research Unit, Saint Mary's Hospital, Mayo Clinic, 1216 Second St. S.W., Rochester, MN 55905, U.S.A.
†Tumor Biology Program, Guggenheim Building, Mayo Clinic, Rochester, MN 55905, U.S.A.,
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Abigail A. CONLEY;
Abigail A. CONLEY
1
∗Gastroenterology Research Unit, Saint Mary's Hospital, Mayo Clinic, 1216 Second St. S.W., Rochester, MN 55905, U.S.A.
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Martin FERNANDEZ ZAPICO;
Martin FERNANDEZ ZAPICO
∗Gastroenterology Research Unit, Saint Mary's Hospital, Mayo Clinic, 1216 Second St. S.W., Rochester, MN 55905, U.S.A.
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Sharon M. DELGADO;
Sharon M. DELGADO
∗Gastroenterology Research Unit, Saint Mary's Hospital, Mayo Clinic, 1216 Second St. S.W., Rochester, MN 55905, U.S.A.
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Jin-San ZHANG;
Jin-San ZHANG
∗Gastroenterology Research Unit, Saint Mary's Hospital, Mayo Clinic, 1216 Second St. S.W., Rochester, MN 55905, U.S.A.
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Raul URRUTIA
Raul URRUTIA
2
∗Gastroenterology Research Unit, Saint Mary's Hospital, Mayo Clinic, 1216 Second St. S.W., Rochester, MN 55905, U.S.A.
†Tumor Biology Program, Guggenheim Building, Mayo Clinic, Rochester, MN 55905, U.S.A.,
‡Department of Biochemistry and Molecular Biology, Guggenheim Building, Mayo Clinic, Rochester, MN 55905, U.S.A.
2To whom correspondence should be addressed (e-mail urrutia.raul@mayo.edu).
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Publisher: Portland Press Ltd
Received:
March 07 2002
Revision Received:
May 20 2002
Accepted:
May 29 2002
Accepted Manuscript online:
May 29 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2002
2002
Biochem J (2002) 366 (3): 873–882.
Article history
Received:
March 07 2002
Revision Received:
May 20 2002
Accepted:
May 29 2002
Accepted Manuscript online:
May 29 2002
Citation
Joanna A. KACZYNSKI, Abigail A. CONLEY, Martin FERNANDEZ ZAPICO, Sharon M. DELGADO, Jin-San ZHANG, Raul URRUTIA; Functional analysis of basic transcription element (BTE)-binding protein (BTEB) 3 and BTEB4, a novel Sp1-like protein, reveals a subfamily of transcriptional repressors for the BTE site of the cytochrome P4501A1 gene promoter. Biochem J 15 September 2002; 366 (3): 873–882. doi: https://doi.org/10.1042/bj20020388
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