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
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
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DOI：
10.1042/bj20020388
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发表时间：
2002-09-15
影响因子：
4.1
通讯作者：
Urrutia, R
中科院分区：
文献类型：
--
作者：
Kaczynski, JA;Conley, AA;Urrutia, R
转录因子的Spl-like家族正在成为参与基因表达控制的细胞机制的组成部分。该蛋白家族的成员含有三个高度同源的C-末端锌指基序，其结合在多种基因的启动子中发现的富含GC的序列，例如致癌物代谢细胞色素P4501 A1（CYP 1A 1）基因的启动子中的基本转录元件（BTE）。在本研究中，我们报告了BTE结合蛋白（BTEB）4的分子和功能特征，BTEB 4是一种新的普遍表达的Sp1样蛋白家族成员。该蛋白代表BTEB 1的新同源物，最初描述为CYP 1A 1基因启动子中BTE位点的调节剂。与最近描述的BTEB 3类似，我们证明了BTEB 4的N-末端区域直接抑制转录并结合辅阻遏物mSin 3A。此外，我们表明，C-末端锌指结构域的BTEB 4结合特异性的BTE网站的CYP 1A 1启动子，类似于BTEB 1和BTEB 3。此外，我们表明，BTEB 3和BTEB 4抑制CYP 1A 1基因启动子通过BTE网站在HepG 2和BxPC 3细胞。因此，这种蛋白的鉴定扩展了参与转录抑制的Sl样蛋白家族的BTEB样成员的库。此外，我们的研究结果表明，BTEB亚家族可以通过BTE位点抑制CYP 1A 1基因启动子。
The Spl-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 Spl-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.