Transcription of Protein-coding Genes in Leishmania

利什曼原虫蛋白质编码基因的转录

• 批准号: 7843539
• 负责人: Peter John Myler
• 金额: $ 48.2万
• 依托单位: SEATTLE BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7843539
• 关键词: Animals; Antibodies; Base Sequence; Binding; Biological Assay; Chromatin; Chromatin Structure; Chromosomes, Human, Pair 1; Code; Complex; Country; DNA; DNA Sequence; DNA-Protein Interaction; Deoxyribonuclease I; Development; Electrophoretic Mobility Shift Assay; Elements; Enhancers; Enzymes; Epigenetic Process; Eukaryota; Gene Cluster; Gene Expression; General Transcription Factors; Genes; Genetic; Genetic Transcription; Genome; Genomics; Histone H3; Histones; Human; In Vitro; Infection; Investigation; Knowledge; Laboratories; Leishmania; Ligands; Location; Maps; Messenger RNA; Methods; Micrococcal Nuclease; Modeling; Molecular; Morbidity - disease rate; Organism; Parasites; Pharmaceutical Preparations; Process; Proteins; Proteolysis; RNA Polymerase II; Recruitment Activity; Research Design; Role; Signal Transduction; Site; System; TATA-Box Binding Protein; Testing; Trans-Splicing; Transcript; Transcription Factor TFIIA; Transcription Factor TFIIB; Transcription Initiation; Transcription Initiation Site; Transcriptional Activation; Transcriptional Regulation; Work; chemotherapeutic agent; chromatin immunoprecipitation; chromatin modification; design; gene replacement; genome-wide; histone acetyltransferase; histone methyltransferase; histone modification; homologous recombination; mortality; novel; promoter; protein reconstitution; research study; transcription factor

Despite more than 20 years of molecular investigation. little is currently known about the essential process of the transcriptioo of protein-coding genes in Leishmania and other trypanosomatids, other than that it differs from that in other eukaryotes because mature mRNAs are generated by transspncing of large polycistronic primary transcripts. Moreover, there is no evidence fO( the transcriptional regulation of gene expression typically seen in other organisms. Previous worK from our laboratory has shown that transcription initiates at ooly a small number of sites between large (50-500 kb) divergent clusters of adjacent protein-coding genes on the same DNA strand and proceeds bi-directionally before temlination at the junction between convergent gene clusters. However, the 'promoter" elements involved in transcription inillation remain a mystery. In other eukaryotes, histone modification and chromatin re-modeling are important for activation of transcription, and recent experiments suggest that this may also be the case in trypanosomatids. This has ted us to hypothesize that the strand-switch regions between divergent PGCs recruit chromatin-remodenng complexes which modify histones and alter the local chromatin structure in these regions to allow access by the RNA polymerase II preinitiation complex, which then initiates transcription in both directions. In this proposal, we will test this hypothesis and build on our current work to further characterize the chromatin-modifying enzymes that are involved in transcription initiation.

尽管进行了20多年的分子研究。目前对利什曼原虫和其他锥虫中蛋白质编码基因转录的基本过程知之甚少，除了它与其他真核生物中的不同之外，因为成熟的mRNA是通过大的多顺反子初级转录物的转位产生的。此外，没有证据表明基因表达的转录调控通常在其他生物体中出现。我们实验室之前的工作表明，转录起始于相邻蛋白质大（50-500 kb）发散簇之间的少数位点。 -编码基因在同一DNA链上，并在会聚基因簇之间的连接处终止之前双向进行。然而，参与转录注入的“启动子”元件仍然是个谜。在真核生物中，组蛋白修饰和染色质重塑对于转录激活很重要，最近的实验表明锥虫中也可能存在这种情况，这让我们假设不同的 PGC 之间的链转换区域会募集染色质重塑复合物。它修饰组蛋白并改变这些区域的局部染色质结构，以允许 RNA 聚合酶 II 预启动复合物进入，然后启动双向转录。在本提案中，我们将测试这一假设，并以我们当前的工作为基础，进一步表征参与转录起始的染色质修饰酶。

项目成果

Characterization of the RNA polymerase II and III complexes in Leishmania major.

大利什曼原虫 RNA 聚合酶 II 和 III 复合物的表征。

• 发表时间: 2007-04
• 影响因子: 4
• 作者: Martínez;Saxena, Alka;Green, Amanda;Leland, Aaron;Myler, Peter J
• 通讯作者: Myler, Peter J

Gene organization and sequence analyses of transfer RNA genes in Trypanosomatid parasites.

锥虫寄生虫中转移 RNA 基因的基因组织和序列分析。

• 发表时间: 2009
• 影响因子: 4.4
• 作者: Padilla;Florencio;Figueroa;Manning;Hernandez;Myler, Peter J;Martinez
• 通讯作者: Martinez

Glucosylated hydroxymethyluracil, DNA base J, prevents transcriptional readthrough in Leishmania.

葡萄糖基化羟甲基尿嘧啶（DNA 碱基 J）可防止利什曼原虫的转录通读。

• 发表时间: 2012-08-31
• 影响因子: 64.5
• 作者: van Luenen, Henri G A M;Farris, Carol;Jan, Sabrina;Genest, Paul;Tripathi, Pankaj;Velds, Arno;Kerkhoven, Ron M;Nieuwland, Marja;Haydock, Andrew;Ramasamy, Gowthaman;Vainio, Saara;Heidebrecht, Tatjana;Perrakis, Anastassis;Pagie, Ludo;van
• 通讯作者: van