Female‐specific gene regulation in malaria parasites by an AP2‐family transcription factor
Female‐specific gene regulation in malaria parasites by an AP2‐family transcription factor
复制标题
DOI：
10.1111/mmi.14334
复制
发表时间：
2020-01
影响因子：
3.6
通讯作者：
M. Yuda;Izumi Kaneko;S. Iwanaga;Yuho Murata;Tomomi Kato
中科院分区：
文献类型：
--
作者：
M. Yuda;Izumi Kaneko;S. Iwanaga;Yuho Murata;Tomomi Kato
疟疾配子母细胞是配子前体，是疟疾传播给蚊子媒介的必要阶段。在脊椎动物宿主的血液中，它发育成成熟的雄性或雌性，能够在蚊子的血液中转化为配子。尽管这一阶段在疟疾生命周期中很重要，但对配子体发育的遗传调控知之甚少。特别是，参与性别特异性基因表达的转录因子尚未确定。在本文中，我们报告了一个AP 2家族转录因子，AP 2-FG，负责女性特异性基因调控。伯氏疟原虫中的AP 2-FG表达仅在雌性配子体中观察到，在发育中的配子体出现性二型之前4-6 h开始。AP 2 ‐FG破坏导致雌性成熟停滞，但不影响雄性发育。染色质免疫沉淀测序分析表明，AP 2-FG直接调控超过700个基因。其靶点包括女性配子体特异性功能的基因，如配子发生，受精和合子发育。与靶基因启动子结合的AP 2-FG与10 bp序列基序相关。这些结果表明，AP 2-FG通过控制雌性特异性基因表达谱，在早期配子体向成熟雌性的分化中发挥作用。
The malaria gametocyte, the gamete precursor, is the essential stage for malaria transmission to the mosquito vector. In the vertebrate host's blood, it develops into a mature male or female capable of transforming into a gamete in the mosquito blood meal. Despite the importance of this stage in the malaria life cycle, the genetic regulation of gametocyte development is poorly understood. In particular, transcription factors involved in sex‐specific gene expression have not been identified. In this paper, we report that an AP2‐family transcription factor, AP2‐FG, is responsible for female‐specific gene regulation. AP2‐FG expression in Plasmodium berghei was observed exclusively in female gametocytes, in the beginning of 4–6 h before sexual dimorphism manifests in developing gametocytes. AP2‐FG disruption resulted in the arrest of female maturation, but did not affect the development of males. Chromatin immunoprecipitation sequencing analysis suggested that AP2‐FG directly regulates over 700 genes. Its targets include genes for female gametocyte‐specific functions, such as gametogenesis, fertilization and zygote development. AP2‐FG binding to target gene promoters was associated with a 10 bp sequence motif. These results indicate that AP2‐FG plays a role in the differentiation of early gametocytes to mature females by governing a female‐specific gene expression repertoire.