Malaria HATs in Transcription Regulation

疟疾的负担日益加重，部分原因是恶性疟原虫的抗药性， 需要新的疗法转录领域的最新研究已经证明了转录因子的功能。 染色质在真核生物基因表达调控中的重要性。调节染色质的酶 结构对控制基因表达有着深远的影响。在这些酶中，组蛋白 乙酰转移酶（HAT），其将乙酰基从乙酰辅酶A转移到N-乙酰辅酶A中的赖氨酸残基。 组蛋白的末端尾是研究得最好的。干扰组蛋白的药物的抗寄生虫作用 乙酰化和我们小组最近对恶性疟原虫染色质重塑因子的研究 表明动态组蛋白乙酰化是转录的重要表观遗传机制 调节，并在疟疾寄生虫的发展中发挥着重要作用。因此，我们建议：（1） 描述两个转录相关的HAT蛋白家族，2）确定它们在全球范围内的功能作用， 转录调控，和3）鉴定恶性疟原虫中多蛋白HAT复合物的亚基。帽子 蛋白质将使用分子和生物化学方法表征，以及它们在寄生虫中的功能。 发育和转录调控将由靶向基因破坏和全基因组 表情分析这项研究旨在揭示转录过程中的表观遗传机制 控制寄生虫发育和毒力的调节。组蛋白的重要性 乙酰化在基因调控中的重要作用以及HAT和组蛋白去乙酰化酶作为药物靶点的巨大潜力 强调这一领域研究的重要性，这可能导致新的抗疟药物。 疟疾仍然是许多国家的一个主要公共卫生问题。它最近的流行率回升是 部分原因是抗药性。这项研究的目的是表征一组酶的功能， 调节寄生虫的基因表达，这可能会导致新的抗疟疾药物的设计。

The increasing burden of malaria, in part, due to drug resistance in the parasite Plasmodium falciparum, demands new therapies. Recent research in the field of transcription has demonstrated the functional importance of chromatin in regulating gene expression in eukaryotes. Enzymes that modulate chromatin structures have a profound effect on controlling gene expression. Among these enzymes, histone acetyltransferases (HATs), which transfer the acetyl group from acetyl-CoA to the lysine residues in the N- terminal tails of histones, are the best studied. The antiparasitic effects of drugs that disturb histone acetylation and recent studies from our group on the chromatin remodeling factors in P.falciparum demonstrated that dynamic histone acetylation is an important epigenetic mechanism of transcription regulation and plays a prominent role in development of the malaria parasite. Thus, we propose to 1) characterize two families of transcription-related HAT proteins, 2) determine their functional roles in global transcription regulation, and 3) identify the subunits of multiprotein HAT complexes in P. falciparum. HAT proteins will be characterized using molecular and biochemical approaches, and their functions in parasite development and transcription regulation will be determined by targeted gene disruption and genome-wide expression analysis. This proposed research aims to reveal the epigenetic mechanisms in transcription regulation that controls the parasite development and virulence. The fundamental importance of histone acetylation in gene regulation and the great potential of HAT and histone deacetylase as drug targets underline the significance of research in this area, which may lead to novel antimalarial drugs. Malaria is still a major public health problem in many countries. Its recent resurgence in prevalence is partially due to drug resistance. This study aims to characterize the functions of a group of enzymes that regulate parasite gene expression, which may lead to the design of novel antimalarial drugs.