Epigenetic factors regulate RNA polymerase II transcription Trypanosoma brucei

描述（由申请人提供）：布鲁氏锥虫是一种单细胞原生动物寄生虫，在非洲部分地区感染人类和牛。感染了布鲁氏杆菌的人会患上一种叫做非洲昏睡病的严重神经系统疾病，如果不及时治疗，可能会在无意中致命。针对这种寄生虫的化疗药物很少，毒性相对较大，并且在后勤上难以施用。因此，迫切需要确定新的药物靶点并开发更好的药物。该提案将确定布鲁氏杆菌基因调控的独特方面，发现作为潜在药物靶点的新机制。与其他真核生物不同，锥虫体内由RNA聚合酶II （Pol II）转录的基因排列在大的多顺反子转录单位（PTU）中，形成长一级RNA。对转录起始或终止的调控知之甚少。然而，最近的证据表明，表观遗传因素，特别是碱基J，一个超修饰的核苷酸在调控Pol II中起着重要作用

DESCRIPTION (provided by applicant): Trypanosoma brucei is a single cell protozoan parasite that infects humans and cattle in parts of Africa. Humans infected with T. brucei suffer from a severe neurological disease called African sleeping sickness that is inadvertently fatal when left untreated. Chemotherapeutic drugs against this parasite are few, relatively toxic, and logistically difficult to administer. The need to identify new drug targets and develop better medications is therefore urgent. This proposal will identify unique aspects of gene regulation in T. brucei, discovering novel mechanisms as potential drug targets. Unlike other eukaryotes, genes transcribed by RNA polymerase II (Pol II) in trypanosomes are arranged in large polycistronic transcription units (PTU) as long primary RNAs. Little is known about regulation of transcription initiation or termination. However, recent evidence indicates that epigenetic factors and especially base J, a hyper-modified nucleotide plays a significant role in regulation of Pol II mediated transcription. We have identified regulation of transcription initiation as well as evidence of regulated transcription termination. I propose two aims to study these modes of repression and the epigenetic mechanisms that are involved.