Genetic Switch Controlled by an Unusual Family of Transcription Activators

由不寻常的转录激活剂家族控制的基因开关

基本信息

项目摘要

The vast majority of living organisms on earth are bacteria, and the vast majority of genetic information is bacterial. Bacteria exchange genes between species at a high rate, but the rules governing this exchange are poorly understood despite their importance for understanding microbial evolution and ecology. Restriction-modification (RM) systems appear to play a central "gatekeeper" role, and their regulation is crucial to both their distribution and the gatekeeper role. A substantial number of RM systems are controlled by small "C proteins" that activate transcription of their own genes and those of the downstream restriction endonucleases; closely-related C proteins have been found in bacteria as different as E. coli and Bacillus. This is surprising for two reasons. First, broad host range is particularly difficult to achieve among transcriptional activators, which must make productive contacts with a range of RNA polymerases. Second, the C proteins are much smaller than typical transcription activators. The regulatory logic and actions of these unusual activators have received only limited characterization, but the structure for a C protein has recently been determined. The understanding of both transcriptional activation and of RM system function will be improved by studying the remarkable C protein family. Four hypotheses will be tested, focusing on a C protein from the enterobacterium Proteus vulgaris (C.PvuII). First is the hypothesis that the requirement for C.PvuII delays expression of the endonuclease gene pvuIIR relative to that for the protective methyltransferase. This would prevent cell death when the RM system genes move into a new bacterium. Second is the hypothesis that asymmetries in the target sequences ("C boxes") serve to modulate C protein binding and affect its behavior as a regulatory switch. Third is the hypothesis that C.PvuII activates transcription via contact to region 4 of RpoD (sigma70), helping to explain the unusually broad host range of the C proteins. Fourth is the hypothesis that C.PvuII and RNA polymerase holoenzyme are necessary and sufficient for in vitro activation of pvuIICR transcription which, again, would help to explain the broad host range. Broader impacts include graduate student training, including their voluntary participation in teaching activities and attendance at national or international meetings; research training of undergraduates and medical students and continued dissemination of data via publication, seminars, and providing links to articles on the P.I.'s academic web site. Indirect impacts would include teaching in the areas of microbial genetics, molecular biology, and bioinformatics; and development of an educational and research program in bioinformatics and proteomics/genomics.
地球上绝大多数活着的有机体是细菌,绝大多数遗传信息是细菌。细菌在物种之间以很高的速度交换基因,但管理这种交换的规则却知之甚少,尽管它们对理解微生物进化和生态学很重要。限制修饰(RM)系统似乎扮演着中心的“看门人”角色,它们的监管对它们的分布和看门人的角色都是至关重要的。相当多的RM系统由激活自身基因转录和下游限制性内切酶转录的小“C蛋白”控制;在不同于大肠杆菌和芽孢杆菌的细菌中发现了密切相关的C蛋白。这令人惊讶,有两个原因。首先,在转录激活剂中实现广泛的宿主范围特别困难,这必须与一系列RNA聚合酶进行有效的接触。其次,C蛋白比典型的转录激活剂小得多。这些不寻常的激活剂的调控逻辑和作用只得到了有限的描述,但C蛋白的结构最近已经确定。通过研究这个重要的C蛋白家族,将有助于提高对转录激活和RM系统功能的理解。将检验四个假设,重点是来自普通变形杆菌(C.PvuII)的一种C蛋白。第一个假设是,对于C.PvuII的需求相对于保护性甲基转移酶的需求延迟了内切酶基因pvuIIR的表达。这将防止当RM系统基因进入新细菌时细胞死亡。第二种假设是,靶序列(“C盒”)中的不对称作用于调节C蛋白结合,并影响其作为调节开关的行为。第三个假设是,C.PvuII通过接触RpoD区域4(Sigma70)来激活转录,这有助于解释C蛋白异常广泛的宿主范围。第四个假设是,C.PvuII和RNA聚合酶全酶是体外激活pvuIICR转录的必要条件和充分条件,这将再次有助于解释广泛的宿主范围。更广泛的影响包括研究生培训,包括自愿参加教学活动和参加国内或国际会议;对本科生和医学生进行研究培训,并通过出版物、研讨会和提供P.I.S学术网站上文章的链接继续传播数据。间接影响包括微生物遗传学、分子生物学和生物信息学领域的教学;以及生物信息学和蛋白质组学/基因组学教育和研究计划的发展。

项目成果

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Robert Blumenthal其他文献

The Cell Biology of HIV-I Entry
  • DOI:
    10.1186/1742-4690-2-s1-s137
  • 发表时间:
    2005-12-08
  • 期刊:
  • 影响因子:
    3.900
  • 作者:
    Robert Blumenthal;Catherine M Finnegan;Mathias Viard;Satinder S Rawat;Anu Puri
  • 通讯作者:
    Anu Puri
The role of the target membrane structure in fusion with Sendai virus.
目标膜结构与仙台病毒融合的作用。
  • DOI:
    10.3109/09687688709029434
  • 发表时间:
    1987
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Debi P. Sarkar;Robert Blumenthal
  • 通讯作者:
    Robert Blumenthal
Laser-Triggered Release of Entrapped Photo-Reactive Solutes from Liposomes Containing Diacetylenic Phosphatidylcholine
  • DOI:
    10.1016/j.bpj.2010.12.2894
  • 发表时间:
    2011-02-02
  • 期刊:
  • 影响因子:
  • 作者:
    Amichai Yavlovich;Darrell B. Tata;Robert Blumenthal;Anu Puri
  • 通讯作者:
    Anu Puri
Mechanisms of Entry of Vaccinia Virus into Cells Studied by Photosensitized Labeling
  • DOI:
    10.1016/j.bpj.2010.12.3634
  • 发表时间:
    2011-02-02
  • 期刊:
  • 影响因子:
  • 作者:
    Mathias Viard;Bernard Moss;Robert Blumenthal
  • 通讯作者:
    Robert Blumenthal
Mutational analysis of HIV-1 gp41 mediated apoptosis and its correlation with fusion/hemifusion
  • DOI:
    10.1186/1742-4690-3-s1-s89
  • 发表时间:
    2006-12-21
  • 期刊:
  • 影响因子:
    3.900
  • 作者:
    Himanshu Garg;Robert Blumenthal
  • 通讯作者:
    Robert Blumenthal

Robert Blumenthal的其他文献

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{{ truncateString('Robert Blumenthal', 18)}}的其他基金

Regulation of Type II Restriction-Modification Systems
II 类限制修改系统的监管
  • 批准号:
    0964728
  • 财政年份:
    2010
  • 资助金额:
    $ 43万
  • 项目类别:
    Continuing Grant
FASEB Conference on Biological Methylation: July 17-22, 1999, Vermont Academy, Saxton's River, VT
FASEB 生物甲基化会议:1999 年 7 月 17-22 日,佛蒙特学院,萨克斯顿河,佛蒙特州
  • 批准号:
    9816744
  • 财政年份:
    1999
  • 资助金额:
    $ 43万
  • 项目类别:
    Standard Grant
Mechanism of Action of an Unusual Mobile Regulatory Cassette: The C Genes of Restriction-Modification Systems
不寻常的移动调节盒的作用机制:限制性修饰系统的 C 基因
  • 批准号:
    9904523
  • 财政年份:
    1999
  • 资助金额:
    $ 43万
  • 项目类别:
    Continuing Grant
How are Restriction Systems Controlled, and How Do They Recognize DNA Sequences?
限制系统是如何控制的,以及它们如何识别 DNA 序列?
  • 批准号:
    9631137
  • 财政年份:
    1996
  • 资助金额:
    $ 43万
  • 项目类别:
    Continuing Grant
Analysis of DNA Sequence Recognition by Three Types of Sequence-Specific Protein
三种序列特异性蛋白的 DNA 序列识别分析
  • 批准号:
    9205248
  • 财政年份:
    1992
  • 资助金额:
    $ 43万
  • 项目类别:
    Continuing Grant
Analysis of DNA Sequence Recognition by Enzymes
酶对 DNA 序列识别的分析
  • 批准号:
    8818673
  • 财政年份:
    1989
  • 资助金额:
    $ 43万
  • 项目类别:
    Continuing Grant
Mathematical Sciences: Research and Workshop in Markov Processes
数学科学:马尔可夫过程研究和研讨会
  • 批准号:
    8601782
  • 财政年份:
    1986
  • 资助金额:
    $ 43万
  • 项目类别:
    Standard Grant
Regulation and Biochemistry of Restriction Endonucleases
限制性内切酶的调控和生物化学
  • 批准号:
    8409652
  • 财政年份:
    1984
  • 资助金额:
    $ 43万
  • 项目类别:
    Continuing Grant
Regulation and Biochemistry of Restriction Endonucleases
限制性内切酶的调控和生物化学
  • 批准号:
    8201953
  • 财政年份:
    1982
  • 资助金额:
    $ 43万
  • 项目类别:
    Standard Grant

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