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Cellular factors maintaining and reversing silencing of bacterial chromatin

维持和逆转细菌染色质沉默的细胞因子

基本信息

批准号：
10583882
负责人：
IRINA ARTSIMOVITCH
金额：
$ 38.83万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-02-01 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10583882
关键词：
Address Antibiotics Bacteria Bacterial Genes Binding Biochemical Biochemistry Biogenesis Biology Cells Chromatin Communities Complex Coupling DNA DNA-Binding Proteins DNA-Directed RNA Polymerase Data Elongation Factor Ensure Environment Enzymes Escherichia coli Exclusion Family Filament Food Funding Gene Expression Gene Expression Regulation Gene Silencing Genes Genetic Genetic Transcription Genomics Growth Habitats Heterochromatin Histones Homologous Gene Hyperactivity In Vitro Interdisciplinary Study Life Maintenance Mediating Molecular Molecular Chaperones Molecular Conformation Molecular Genetics Nature Nucleoproteins Nutrient Operon Phylogenetic Analysis Positioning Attribute Productivity Proteins Proteomics RNA RNA chemical synthesis Regulation Research Personnel Rho Factor Source Stress Structure Transcription Elongation Transcription Initiation Translating Translations Travel Virulence Factors Work biological adaptation to stress cell envelope experimental study gene repression genome-wide in vivo insight paralogous gene promoter repaired rho termination factor tool transcription termination

项目摘要

All living cells possess mechanisms that partition the chromosomal DNA into actively transcribed, accessible domains, and transcriptionally silent domains densely packed by DNA-bound proteins. In Escherichia coli, nucleoid-associated proteins (NAPs) assemble into nucleoprotein filaments that cover several kilobase-long regions of DNA, silencing expression of horizontally acquired xenogenes, virulence factors or enzymes needed for utilization of exotic nutrients. While silencing of promoters, frequently by exclusion of RNA polymerase, is well studied, silencing during RNA chain elongation has only recently come to light. E. coli H-NS and its homolog StpA are NAPs that directly bind to AT-rich DNA and inhibit transcription initiation and elongation. The available data show that the transcription elongation complex is involved in both maintenance and relief of NAP-mediated silencing. Recent data implicate the ω subunit of RNA polymerase in regulation of global DNA topology and transcription of xenogeneic regions. A universally conserved elongation factor, NusG, and termination factor Rho, which are associated with RNA polymerase genome-wide and stop synthesis of RNAs that are not actively translated, cooperate with H-NS to silence xenogenes and other inactive genes. Conversely, we showed that a specialized NusG paralog, RfaH, which is required for expression of xenogeneic operons, excludes NusG and Rho from the transcribing RNA polymerase and counteracts NAP-mediated silencing. We propose to elucidate molecular mechanisms which control the accessibility of bacterial chromatin, focusing on poorly understood regulation during transcription elongation. In Aim 1, we will investigate effects of the ubiquitous ω subunit on RNA polymerase structure and activity. We will identify cellular factors that interact with ω using genetics and proteomics, characterize ω-induced changes in transcription complexes, and investigate ω effects on in vitro RNA synthesis. In Aim 2, we will study regulation of Rho- dependent termination. We posit that hyperactive Rho may be harmful during slow growth or translational stress and will investigate mechanisms by which Rho activity may be globally downregulated, e.g., by changing Rho conformation, promoting the formation of inactive Rho filaments, or blocking Rho binding to RNA. In Aim 3, we will identify new factors that contribute to maintenance of E. coli heterochromatin; determine contributions of different NAPs, Rho, and ω to silencing; and elucidate the molecular mechanism by which RfaH counter-silences NAPs in vitro.

所有活细胞都具有将染色体DNA分割成活跃转录，

项目成果

期刊论文数量（95）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

CBR antimicrobials alter coupling between the bridge helix and the β subunit in RNA polymerase.

DOI：
10.1038/ncomms4408
发表时间：
2014-03-06
期刊：
NATURE COMMUNICATIONS
影响因子：
16.6
作者：
Malinen, Anssi M.;NandyMazumdar, Monali;Turtola, Matti;Malmi, Henri;Grocholski, Thadee;Artsimovitch, Irina;Belogurov, Georgiy A.
通讯作者：
Belogurov, Georgiy A.

Initial events in bacterial transcription initiation.