尚未确定:恶性疟原虫组蛋白赖氨酸甲基转移酶。

IF 3.8 2区 医学 Q2 CHEMISTRY, MEDICINAL
Disha Shah, Krishanpal Karmodiya
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引用次数: 0

摘要

恶性疟原虫引起的疟疾仍然是一项全球卫生挑战。它的预防、治疗和消除努力受到对目前有效治疗方案不可避免地出现耐药性的威胁。具有不同作用方式和多阶段、多物种活性的新型抗疟药将是对抗疟原虫军备竞赛的重要补充。恶性疟原虫的表观基因组在这场战斗中代表了一个有希望的目标,并为有针对性的干预提供了令人兴奋的机会。具有异常丰富的at基因组,特异性转录因子的相对缺乏和有限的异染色质,表观遗传控制已成为恶性疟原虫生存和毒力的重要贡献者。恶性疟原虫组蛋白被动态标记为大量的翻译后修饰。其中包括一些研究得很好的标记和一些新的标记。寄生虫具有与其宿主不同的表观遗传特征,并表现出几种寄生虫特有的适应性。然而,这些标志的监管机构仍未得到充分研究。虽然组蛋白乙酰化及其调控因子已经在该领域得到了更广泛的研究,但对其他表观遗传效应的研究也在追赶。本文综述了旨在了解寄生虫组蛋白赖氨酸甲基转移酶在形成转录调控和组蛋白修饰景观中的作用的研究工作。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Yet to SET: Plasmodium falciparum Histone Lysine Methyltransferases.

Malaria caused by Plasmodium falciparum continues to remain a global health challenge. Its prevention, treatment and elimination efforts are threatened by the inevitable emergence of drug resistance to currently effective treatment regimes. New antimalarials with distinct modes of action and multistage and multispecies activity will be an important addition to the arms race against the malarial parasite. P. falciparum's epigenome represents a promising target in this battle and offers exciting opportunities for targeted intervention. With an unusually AT-rich genome, a relative paucity of specific transcription factors and limited heterochromatin, epigenetic control has emerged as an important contributor to P. falciparum's survival and virulence. P. falciparum histones are marked dynamically with a vast array of post translational modifications. These include several well studied and some novel marks. The parasite has an epigenetic signature distinct from its host and shows several parasite-specific adaptations. The regulators of these marks remain understudied, however. While histone acetylation and its regulators have been more extensively studied in the field, research on other epigenetic effectors is also catching up. This review highlights the research efforts aimed at understanding the role of the parasite's histone lysine methyltransferases in shaping transcriptional regulation and the histone modification landscape.

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来源期刊
ACS Infectious Diseases
ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES
CiteScore
9.70
自引率
3.80%
发文量
213
期刊介绍: ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.
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