Differentiation of Plasmodium male gametocytes is initiated by the recruitment of a chromatin remodeler to a male-specific cis-element.
Differentiation of Plasmodium male gametocytes is initiated by the recruitment of a chromatin remodeler to a male-specific cis-element.
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DOI：
10.1073/pnas.2303432120
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发表时间：
2023-05-16
影响因子：
11.1
通讯作者：
Yuda, Masao
中科院分区：
文献类型：
--
作者：
Kaneko, Izumi;Nishi, Tsubasa;Iwanaga, Shiroh;Yuda, Masao
疟原虫配子母细胞是配子的前体，在疟原虫向蚊媒传播中起核心作用。雄配子母细胞在蚊子的血粉中转化为多个能动的雄配子，并迅速与雌配子融合。雄性配子体的转录组由基因组复制和基于鞭毛的运动性的基因组成，反映了它们在产生多个雄性配子中的作用。在这里，我们报告说，配子体特异性染色质重塑在建立这种独特的基因表达谱，通过创建这些基因的上游无核小体区域中起着至关重要的作用。我们报告说，染色质重塑是疟原虫生命周期中阶段转换的第一步。疟原虫是疟疾的病原体，具有复杂的生命周期;然而，涉及细胞类型变化的基因调控机制仍然未知。在这里，我们报告，配子体蔗糖非发酵2（gSNF 2），SNF 2样染色质重塑ATP酶，在雄性配子体的分化中起着至关重要的作用。在破坏gSNF 2后，雄性配子母细胞丧失发育成配子的能力。ChIP-seq分析显示，gSNF 2通过一个五碱基的雄性特异性顺式作用元件广泛募集到雄性特异性基因的上游。在gSNF 2破坏的寄生虫中，超过100个靶基因的表达显著降低。ATAC-seq分析表明，这些基因的表达降低与这些基因上游的无核小体区域的减少相关。这些结果表明，gSNF 2诱导的染色质景观的全球变化是从早期配子体雄性分化的第一步。这项研究提供了可能性，染色质重塑是负责疟原虫生命周期中的细胞类型的变化。
Plasmodium gametocytes, precursors of gametes, play a central role in parasite transmission to the mosquito vector. Male gametocytes transform into multiple motile male gametes in the blood meal of a mosquito and promptly fuse with female gametes. The transcriptome of male gametocytes consists of genes for genome replication and flagella-based motility, reflecting their roles in generating multiple male gametes. Here, we report that a gametocyte-specific chromatin remodeler plays a critical role in establishing this unique gene expression repertoire by creating nucleosome-free regions upstream of these genes. We report that chromatin remodeling is an initial step in stage conversion in the Plasmodium lifecycle. Plasmodium parasites, the causative agents of malaria, possess a complex lifecycle; however, the mechanisms of gene regulation involved in the cell-type changes remain unknown. Here, we report that gametocyte sucrose nonfermentable 2 (gSNF2), an SNF2-like chromatin remodeling ATPase, plays an essential role in the differentiation of male gametocytes. Upon disruption of gSNF2, male gametocytes lost the capacity to develop into gametes. ChIP-seq analyses revealed that gSNF2 is widely recruited upstream of male-specific genes through a five-base, male-specific cis-acting element. In gSNF2-disrupted parasites, expression of over a hundred target genes was significantly decreased. ATAC-seq analysis demonstrated that decreased expression of these genes correlated with a decrease of the nucleosome-free region upstream of these genes. These results suggest that global changes induced in the chromatin landscape by gSNF2 are the initial step in male differentiation from early gametocytes. This study provides the possibility that chromatin remodeling is responsible for cell-type changes in the Plasmodium lifecycle.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
9.2
作者：
Hirai, Makoto;Arai, Meiji;Matsuoka, Hiroyuki
通讯作者：
Matsuoka, Hiroyuki
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.5
作者：
Billker, O;Dechamps, S;Brinkmann, V
通讯作者：
Brinkmann, V
DOI：
10.2741/4038
发表时间：
2012-06-01
期刊：
Frontiers in bioscience (Landmark edition)
影响因子：
--
作者：
Byrd AK;Raney KD
通讯作者：
Raney KD