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Arnaud Chastanet Dennis Vitkup Guo-Cheng Yuan Thomas M. Norman Jun S. Liu Richard M. Losick 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(18):8486-8491
A model system for investigating how developmental regulatory networks determine cell fate is spore formation in Bacillus subtilis. The master regulator for sporulation is Spo0A, which is activated by phosphorylation via a phosphorelay that is subject to three positive feedback loops. The ultimate decision to sporulate is, however, stochastic in that only a portion of the population sporulates even under optimal conditions. It was previously assumed that activation of Spo0A and hence entry into sporulation is subject to a bistable switch mediated by one or more feedback loops. Here we reinvestigate the basis for bimodality in sporulation. We show that none of the feedback loops is rate limiting for the synthesis and phosphorylation of Spo0A. Instead, the loops ensure a just-in-time supply of relay components for rising levels of phosphorylated Spo0A, with phosphate flux through the relay being limiting for Spo0A activation and sporulation. In addition, genes under Spo0A control did not exhibit a bimodal pattern of expression as expected for a bistable switch. In contrast, we observed a highly heterogeneous pattern of Spo0A activation that increased in a nonlinear manner with time. We present a computational model for the nonlinear increase and propose that the phosphorelay is a noise generator and that only cells that attain a threshold level of phosphorylated Spo0A sporulate. 相似文献
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Noirot-Gros MF Velten M Yoshimura M McGovern S Morimoto T Ehrlich SD Ogasawara N Polard P Noirot P 《Proceedings of the National Academy of Sciences of the United States of America》2006,103(7):2368-2373
The regulation of initiation of DNA replication is crucial to ensure that the genome is replicated only once per cell cycle. In the Gram-positive bacterium Bacillus subtilis, the function of the YabA protein in initiation control was assigned based on its interaction with the DnaA initiator and the DnaN sliding clamp in the yeast two-hybrid and on the overinitiation phenotype observed in a yabA null strain. However, YabA is unrelated to known regulators of initiation and interacts with several additional proteins that could also be involved directly or not in initiation control. Here, we investigated the specific role of YabA interactions with DnaA and DnaN in initiation control by identifying single amino acid changes in YabA that disrupted solely the interaction with DnaA or DnaN. These disruptive mutations delineated specific interacting surfaces involving a Zn2+-cluster structure in YabA. In B. subtilis, these YabA interaction mutations abolished both initiation control and the formation of YabA foci at the replication factory. Upon coexpression of deficient YabA mutants, mixed oligomers formed foci at the replisome and restored initiation control, indicating that YabA acts within a heterocomplex with DnaA and DnaN. In agreement, purified YabA oligomerized and formed complexes with DnaA and DnaN. These findings underscore the functional association of YabA with the replication machinery, indicating that YabA regulates initiation through coupling with the elongation of replication. 相似文献
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Autoregulation of antibiotic biosynthesis by binding of the end product to an atypical response regulator 下载免费PDF全文
Linqi Wang Xiuyun Tian Juan Wang Haihua Yang Keqiang Fan Gangming Xu Keqian Yang Huarong Tan 《Proceedings of the National Academy of Sciences of the United States of America》2009,106(21):8617-8622
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Cloning and heterologous expression of a gene cluster for the biosynthesis of tetracenomycin C, the anthracycline antitumor antibiotic of Streptomyces glaucescens. 总被引:13,自引:1,他引:13 下载免费PDF全文
H Motamedi C R Hutchinson 《Proceedings of the National Academy of Sciences of the United States of America》1987,84(13):4445-4449
Through complementation of mutations specifically blocking the biosynthesis of tetracenomycin C by Streptomyces glaucescens and selecting for resistance to tetracenomycin C in Streptomyces lividans, all of the genes for the production of tetracenomycin C were inserted in pIJ702, a high copy-number Streptomyces gene cloning vector. The tcm biosynthetic and resistance genes occur as a single cluster in the S. glaucescens genome and are expressed in heterologous streptomycete hosts like S. lividans, resulting in the overproduction of pigmented intermediates of the tetracenomycin C biosynthetic pathway. 相似文献
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Ryan Webb Jonathan D. Wren Matlock Jeffries Jennifer A. Kelly Kenneth M. Kaufman Yuhong Tang Mark Barton Frank Joan Merrill Robert P. Kimberly Jeffrey C. Edberg Rosalind Ramsey‐Goldman Michelle Petri John D. Reveille Graciela S. Alarcn Luis M. Vil Marta E. Alarcn‐Riquelme Judith A. James Timothy J. Vyse Kathy L. Moser Patrick M. Gaffney Gary S. Gilkeson John B. Harley Amr H. Sawalha 《Arthritis \u0026amp; Rheumatology》2009,60(4):1076-1084
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MecB of Bacillus subtilis, a member of the ClpC ATPase family, is a pleiotropic regulator controlling competence gene expression and growth at high temperature. 总被引:16,自引:2,他引:16 下载免费PDF全文
T Msadek F Kunst G Rapoport 《Proceedings of the National Academy of Sciences of the United States of America》1994,91(13):5788-5792
The Bacillus subtilis DegS-DegU histidine kinase-response regulator pair controls the expression of genes encoding degradative enzymes such as levansucrase (sacB) and of genes involved in genetic competence. The mecA and mecB mutations were previously isolated as allowing competence gene expression in complex media. We have shown that the mec mutations also lead to overexpression of sacB, bypassing the DegS-DegU requirement. This expression was shown to be entirely dependent upon ComK, a positive regulator of competence gene expression. The mecB gene was cloned and its nucleotide sequence was determined. The predicted MecB protein show very high similarity over its entire length with members of the ClpC family of ATPases (60% identity). MecB is essential for growth of B. subtilis at high temperature. MecB also acts as a negative regulator of ComK synthesis, thus preventing late competence gene expression. We suggest that under these conditions MecB may interact with MecA to sequester or otherwise inactivate ComK. In response to an unknown signal, active ComK would accumulate through a positive feedback loop, leading to expression of competence genes allowing DNA uptake. 相似文献
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Blue light-induced transcription of plastid-encoded psbD gene is mediated by a nuclear-encoded transcription initiation factor, AtSig5 下载免费PDF全文
Tsunoyama Y Ishizaki Y Morikawa K Kobori M Nakahira Y Takeba G Toyoshima Y Shiina T 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(9):3304-3309
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Effects of estrogen on gene expression in chick oviduct: nuclear receptor levels and initiation of transcription. 总被引:5,自引:0,他引:5 下载免费PDF全文
S Y Tsai M J Tsai R Schwartz M Kalimi J H Clark B W O''''Malley 《Proceedings of the National Academy of Sciences of the United States of America》1975,72(11):4228-4232
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Barley grain with adhering hulls is controlled by an ERF family transcription factor gene regulating a lipid biosynthesis pathway 总被引:2,自引:0,他引:2
Taketa S Amano S Tsujino Y Sato T Saisho D Kakeda K Nomura M Suzuki T Matsumoto T Sato K Kanamori H Kawasaki S Takeda K 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(10):4062-4067
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Control of developmental transcription factor sigma F by sporulation regulatory proteins SpoIIAA and SpoIIAB in Bacillus subtilis. 下载免费PDF全文
R Schmidt P Margolis L Duncan R Coppolecchia C P Moran Jr R Losick 《Proceedings of the National Academy of Sciences of the United States of America》1990,87(23):9221-9225
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Nucleotide sequences of the sporulation gene spo0A and its mutant genes of Bacillus subtilis 总被引:16,自引:3,他引:13 下载免费PDF全文
Jun Kudoh Toshihiko Ikeuchi 《Proceedings of the National Academy of Sciences of the United States of America》1985,82(9):2665-2668
We have determined the nucleotide sequence of a 2375-base-pair DNA fragment, which contained the sporulation gene spo0A cloned from Bacillus subtilis. The sequence had only one long open reading frame consisting of 239 codons, which was found to correspond to the spo0A gene by comparing the nucleotide sequence of the wild-type gene with those of the mutant alleles. The calculated molecular weight of the product of the wild-type spo0A gene was 26,500. We found also a new mutation, sgi, which maps within the spo0A gene. This mutation relieves the growth inhibition of the host cells caused by a multicopy plasmid carrying the spo0A gene. The mutations spo0A12, spo0C9V, and sgi-1 were found to be an amber mutation at the 62nd codon, a missense at the 229th codon, and a frame-shift at the 223rd codon of the spo0A gene, respectively. 相似文献