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The PfAP2-G2 transcription factor is a critical regulator of gametocyte maturation
Molecular Microbiology ( IF 2.6 ) Pub Date : 2020-12-25 , DOI: 10.1111/mmi.14676
Suprita Singh 1, 2 , Joana M Santos 1, 2 , Lindsey M Orchard 1, 2 , Naomi Yamada 3 , Riëtte van Biljon 1, 2, 3 , Heather J Painter 1, 2 , Shaun Mahony 1, 3 , Manuel Llinás 1, 2, 3, 4
Affiliation  

Differentiation from asexual blood stages to mature sexual gametocytes is required for the transmission of malaria parasites. Here, we report that the ApiAP2 transcription factor, PfAP2-G2 (PF3D7_1408200) plays a critical role in the maturation of Plasmodium falciparum gametocytes. PfAP2-G2 binds to the promoters of a wide array of genes that are expressed at many stages of the parasite life cycle. Interestingly, we also find binding of PfAP2-G2 within the gene body of almost 3,000 genes, which strongly correlates with the location of H3K36me3 and several other histone modifications as well as Heterochromatin Protein 1 (HP1), suggesting that occupancy of PfAP2-G2 in gene bodies may serve as an alternative regulatory mechanism. Disruption of pfap2-g2 does not impact asexual development, but the majority of sexual parasites are unable to mature beyond stage III gametocytes. The absence of pfap2-g2 leads to overexpression of 28% of the genes bound by PfAP2-G2 and none of the PfAP2-G2 bound genes are downregulated, suggesting that it is a repressor. We also find that PfAP2-G2 interacts with chromatin remodeling proteins, a microrchidia (MORC) protein, and another ApiAP2 protein (PF3D7_1139300). Overall our data demonstrate that PfAP2-G2 establishes an essential gametocyte maturation program in association with other chromatin-related proteins.

中文翻译:


PfAP2-G2 转录因子是配子体成熟的关键调节因子



疟疾寄生虫的传播需要从无性血液阶段分化为成熟的有性配子细胞。在这里,我们报告 ApiAP2 转录因子 PfAP2-G2 (PF3D7_1408200) 在恶性疟原虫配子细胞的成熟中发挥着关键作用。 PfAP2-G2 与在寄生虫生命周期的许多阶段表达的多种基因的启动子结合。有趣的是,我们还发现 PfAP2-G2 在近 3,000 个基因的基因体中结合,这与 H3K36me3 和其他几个组蛋白修饰以及异染色质蛋白 1 (HP1) 的位置密切相关,表明 PfAP2-G2 在基因体可以作为替代的调控机制。 pfap2-g2的破坏不会影响无性发育,但大多数性寄生虫无法成熟到超过 III 期配子体。 pfap2-g2的缺失导致 28% 的 PfAP2-G2 结合基因过度表达,并且 PfAP2-G2 结合基因没有一个被下调,这表明它是一种阻遏蛋白。我们还发现 PfAP2-G2 与染色质重塑蛋白、微睾 (MORC) 蛋白和另一种 ApiAP2 蛋白 (PF3D7_1139300) 相互作用。总体而言,我们的数据表明 PfAP2-G2 与其他染色质相关蛋白相关,建立了重要的配子体成熟程序。
更新日期:2020-12-25
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