Novel basic-region helix-loop-helix transcription factor (AnBH1) of Aspergillus nidulans counteracts the CCAAT-binding complex AnCF in the promoter of a penicillin biosynthesis gene
Novel basic-region helix-loop-helix transcription factor (AnBH1) of Aspergillus nidulans counteracts the CCAAT-binding complex AnCF in the promoter of a penicillin biosynthesis gene
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DOI：
10.1016/s0022-2836(02)00965-8
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发表时间：
2002-10-25
影响因子：
5.6
通讯作者：
Brakhage, AA
中科院分区：
文献类型：
--
作者：
Caruso, ML;Litzka, O;Brakhage, AA
CCAAT顺式作用元件广泛存在于真核生物的启动子区域。许多在启动子中包含这些元件的基因都受到保守的多聚体CCAAT结合复合体的调控。在真菌中，该复合体被命名为AnCF(A.nidulans CCAAT结合因子)。Ancf调节几个基因，包括青霉素生物合成基因IPNA和AATA。由于据估计，CCAAT结合复合体调节200多个基因，因此一个重要的问题涉及到调节机制，即允许单个复合体以基因特异性的方式调节如此多的基因。这个问题的答案之一似乎在于Ancf与其他转录因子的相互作用。在这里，我们分离到了一个新的转录因子，命名为AnBH1。克隆了相应的anbH1基因，发现该基因位于第四染色体上。该蛋白属于碱性区域螺旋-环-螺旋(BHLH)转录因子家族。AnBH1在体外以同源二聚体的形式与AATA启动子内的不对称E-box结合，该E-box与Ancf结合部位重叠。这是第一个证明CCAAT结合复合体和bHLH转录因子与重叠位点结合的报告。由于anbH1的缺失似乎是致命的，anbH1基因被可调控的alcAp-anbH1基因融合所取代。对该菌株中aatAp-LacZ表达的分析表明，AnBH1是AATA基因表达的抑制子，因此抵消了AncF的积极作用。(C)2002爱思唯尔科学有限公司。保留所有权利。
Cis-acting CCAAT elements are found frequently in eukaryotic promoter regions. Many of the genes containing such elements in their promoters are regulated by a conserved multimeric CCAAT-binding complex. In the fungus Emericella (Aspergillus) nidulans, this complex was designated AnCF (A. nidulans CCAAT-binding factor). AnCF regulates several genes, including the penicillin biosynthesis genes ipnA and aatA. Since it is estimated that the CCAAT-binding complex regulates more than 200 genes, an important question concerns the regulation mechanism that allows so many genes to be regulated by a single complex in a gene-specific manner. One of the answers to this question appears to lie in the interaction of AnCF with other transcription factors. Here, a novel transcription factor designated AnBH1 was isolated. The corresponding anbH1 gene was cloned and found to be located on chromosome IV. The deduced AnBH1 protein belongs to the family of basic-region helix-loop-helix (bHLH) transcription factors. AnBH1 binds in vitro as a homodimer to an, not previously described, asymmetric E-box within the aatA promoter that overlaps with the AnCF-binding site. This is the first report demonstrating that the CCAAT-binding complex and a bHLH transcription factor bind to overlapping sites. Since deletion of anbH1 appears to be lethal, the anbH1 gene was replaced by a regulatable alcAp-anbH1 gene fusion. The analysis of aatAp-lacZ expression in such a strain indicated that AnBH1 acts as a repressor of aatA gene expression and therefore counteracts the positive action of AnCF. (C) 2002 Elsevier Science Ltd. All rights reserved.