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, Abigail A. Conley, Martin E Fernandez-Zapico, Sharon M. Delgado, Jin San Zhang, Raul Urrutia

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)873-882
Number of pages10
JournalBiochemical Journal
Volume366
Issue number3
DOIs
StatePublished - Sep 15 2002

Fingerprint

Functional analysis
Transcription
Cytochromes
Carrier Proteins
Genes
Zinc Fingers
Proteins
GC Rich Sequence
Co-Repressor Proteins
Zinc
Hep G2 Cells
Carcinogens
Transcription Factors
Gene expression
Gene Expression
Machinery

Keywords

  • Carcinogen metabolism
  • GC-rich promoter
  • mSin3A
  • Repression
  • Zinc-finger protein

ASJC Scopus subject areas

  • Biochemistry

Cite this

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. / Kaczynski, Joanna A.; Conley, Abigail A.; Fernandez-Zapico, Martin E; Delgado, Sharon M.; Zhang, Jin San; Urrutia, Raul.

In: Biochemical Journal, Vol. 366, No. 3, 15.09.2002, p. 873-882.

Research output: Contribution to journalArticle

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abstract = "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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AU - Kaczynski, Joanna A.

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AU - Zhang, Jin San

AU - Urrutia, Raul

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