Autorepression of AdpA of the AraC/XylS family, a key transcriptional activator in the A-factor regulatory cascade in Streptomyces griseus

Autorepression of AdpA of the AraC/XylS family, a key transcriptional activator in the A-factor regulatory cascade in Streptomyces griseus
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DOI:
10.1016/j.jmb.2005.04.058
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发表时间:
2005-07-01
影响因子:
5.6
通讯作者:
Horinouchi, S
Horinouchi, S
中科院分区:
生物学2区
文献类型:
--
作者:
Kato, J;Ohnish, Y;Horinouchi, S

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AdpA属于AraC/XylS家族,是灰色链霉菌A因子调控级联中的关键转录激活因子,激活生理和形态分化所需的许多基因。另一方面,AdpA通过与含有多个操纵子位点的启动子区域合作结合来抑制自身的转录。adpA含有三个操纵位点,位点1大约位于核苷酸位置-100处,位点2位于启动子元件处,位点3位于位置+80处。与强结合位点1结合的AdpA增加了弱结合位点2对AdpA的亲和力,可能是通过两个AdpA二聚体分子形成DNA环,从而阻止RNA聚合酶进入启动子。AdpA结合位点3,而弱的亲和力抑制adpA启动子活性独立的网站1和2,可能阻止RNA聚合酶链延长。与该模型一致,含有突变位点I或位点3的adpA的体内转录大大增加。此外,链霉素生产,由AdpA控制的表型之一,大大增加了在站点1和站点3的突变含有adpA的突变体。含有突变位点1的adpA的体外转录也增加。因此,adpA的转录,编码一个重要的转录因子,为有序的生理和形态发育,是自我控制的。(c)2005爱思唯尔有限公司保留所有权利。
AdpA belonging to the AraC/XylS family is a key transcriptional activator in the A-factor regulatory cascade in Streptomyces griseus, activating a number of genes required for physiological and morphological differentiation. On the other hand, AdpA repressed its own transcription by cooperative binding to the promoter region containing multiple operator sites. adpA contained three operator sites, site 1 approximately at nucleotide position -100, site 2 at the promoter elements, and site 3 at position +80. AdpA bound to a strong binding site 1 increased the affinity for AdpA of a weak site 2, probably by forming a DNA loop via the two molecules of AdpA dimer, thus preventing RNA polymerase from access to the promoter. AdpA bound to site 3 with rather weak affinity repressed the adpA promoter activity independently of sites 1 and 2, perhaps preventing RNA polymerase from chain elongation. Consistent with this model, the in vivo transcription of adpA containing mutated site I or site 3 was greatly increased. In addition, streptomycin production, one of the phenotypes controlled positively by AdpA, was greatly increased in the mutants containing adpA with a mutation at site 1 and site 3. The in vitro transcription of adpA containing mutated site 1 was also increased. Thus, the transcription of adpA, encoding an important transcriptional factor for ordered physiological and morphological development, is self-controlled. (c) 2005 Elsevier Ltd. All rights reserved.