Epigenetic factors regulate RNA polymerase II transcription Trypanosoma brucei

描述（由申请方提供）：布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T.布氏病是一种严重的神经系统疾病，称为非洲昏睡病，如果不及时治疗，会致命。针对这种寄生虫的化学药物很少，毒性相对较大，并且难以管理。因此，迫切需要确定新的药物靶点并开发更好的药物。这一建议将确定独特的方面的基因调控T。布氏杆菌，发现新的机制作为潜在的药物靶点。 与其他真核生物不同，在锥虫中由RNA聚合酶II（Pol II）转录的基因以大的多顺反子转录单位（PTU）排列为长的初级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，一种高度修饰的核苷酸，在Pol II的调节中起着重要作用 介导的转录我们已经确定了转录起始的调节以及调节转录终止的证据。我提出了两个目标，研究这些模式的镇压和表观遗传机制所涉及的。

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.