A novel bifunctional histone protein in Streptomyces: a candidate for structural coupling between DNA conformation and transcription during development and stress?

A novel bifunctional histone protein in Streptomyces: a candidate for structural coupling between DNA conformation and transcription during development and stress?
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DOI:
10.1093/nar/gkt180
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发表时间:
2013-05
影响因子:
14.9
通讯作者:
Dyson P
Dyson P
中科院分区:
生物学2区
文献类型:
--
作者:
Aldridge M;Facey P;Francis L;Bayliss S;Del Sol R;Dyson P

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抗生素产生链霉菌是复杂的细菌,在发育过程中重塑全球转录模式及其类核。在这里,我们描述了一种新的发育调节的核苷酸相关蛋白,DdbA,由一个N-末端DNA结合组蛋白H1样结构域和一个C-末端DksA样结构域,可以潜在地调节RNA聚合酶的活性与ppGpp的属。由于其N端结构域,该蛋白可以在体外有效地结合和浓缩DNA。这种DNA结合蛋白功能的丧失导致发育过程中DNA凝聚和响应渗透胁迫调节DNA超螺旋的能力的变化。对DdbA的DksA样活性的初步分析表明,该蛋白的过表达抑制了不能合成ppGpp的relA突变体的抗生素生产的条件性缺陷,就像大肠杆菌中的DksA过表达可以抑制ppGpp 0表型一样。无效突变体也是敏感的氧化应激,由于受损的sigR的转录上调,编码一个替代西格玛因子。因此,我们提出这种双功能组蛋白样蛋白作为一个候选人,可以在结构上耦合链霉菌生命周期中的DNA构象和转录的变化,并响应于压力。
Antibiotic-producing Streptomyces are complex bacteria that remodel global transcription patterns and their nucleoids during development. Here, we describe a novel developmentally regulated nucleoid-associated protein, DdbA, of the genus that consists of an N-terminal DNA-binding histone H1-like domain and a C-terminal DksA-like domain that can potentially modulate RNA polymerase activity in conjunction with ppGpp. Owing to its N-terminal domain, the protein can efficiently bind and condense DNA in vitro. Loss of function of this DNA-binding protein results in changes in both DNA condensation during development and the ability to adjust DNA supercoiling in response to osmotic stress. Initial analysis of the DksA-like activity of DdbA indicates that overexpression of the protein suppresses a conditional deficiency in antibiotic production of relA mutants that are unable to synthesise ppGpp, just as DksA overexpression in Escherichia coli can suppress ppGpp0 phenotypes. The null mutant is also sensitive to oxidative stress owing to impaired upregulation of transcription of sigR, encoding an alternative sigma factor. Consequently, we propose this bifunctional histone-like protein as a candidate that could structurally couple changes in DNA conformation and transcription during the streptomycete life-cycle and in response to stress.
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