The PfAP2-G2 transcription factor is a critical regulator of gametocyte maturation.

The PfAP2-G2 transcription factor is a critical regulator of gametocyte maturation.
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DOI:
10.1111/mmi.14676
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发表时间:
2021-05
影响因子:
3.6
通讯作者:
Llinás M
Llinás M
中科院分区:
生物学2区
文献类型:
--
作者:
Singh S;Santos JM;Orchard LM;Yamada N;van Biljon R;Painter HJ;Mahony S;Llinás M

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疟原虫的传播需要从无性生殖的血液阶段分化为成熟的有性配子体。在这里,我们报告的ApiAP 2转录因子,PfAP 2-G2(PF3D7_1408200)在恶性疟原虫配子体的成熟中起着至关重要的作用。PfAP 2-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PfAP 2-G2在近3000个基因的基因体中结合,这与H3 K36 me 3和其他几种组蛋白修饰以及异染色质蛋白1(HP 1)的位置密切相关,表明PfAP 2-G2在基因体中的占据可能作为另一种调节机制。pfap 2-g2的破坏不影响无性发育,但大多数有性寄生虫无法成熟超过III期配子体。pfap 2-g2的缺失导致28%的PfAP 2-G2结合基因的过表达,并且没有PfAP 2-G2结合基因被下调,表明其是阻遏物。我们还发现PfAP 2-G2与染色质重塑蛋白、一种微睾(MORC)蛋白和另一种ApiAP 2蛋白(PF3D7_1139300)相互作用。总体而言,我们的数据表明,PfAP 2-G2建立了一个必要的配子体成熟程序与其他染色质相关蛋白。
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 3000 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.
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