Characterization of the accessible genome in the human malaria parasite Plasmodium falciparum.
Characterization of the accessible genome in the human malaria parasite Plasmodium falciparum.
复制标题
DOI：
10.1093/nar/gky643
复制
发表时间：
2018-10-12
影响因子：
14.9
通讯作者：
Gómez-Díaz E
中科院分区：
文献类型：
--
作者：
Ruiz JL;Tena JJ;Bancells C;Cortés A;Gómez-Skarmeta JL;Gómez-Díaz E
人类疟疾是一种毁灭性的疾病，也是资源有限国家贫困的主要原因。为了在宿主体内发展和适应，恶性疟原虫经历了基因表达的剧烈变化。为了确定寄生虫基因组中的调节区，我们通过使用转座酶可及染色质测序分析(ATAC-seq)，在红细胞内周期的四个发育阶段对两个培养适应的等基因亚克隆的染色质可及性进行了全基因组分析。TN5转座酶高敏感位点(THSS)优先定位于转录起始点(TSS)。ATAC-seq的染色质可及性预示着活跃的转录以及组蛋白标记H3K9ac和H3K4me3的水平。我们的分析允许识别新的调节区，包括TSS和增强子样元件。我们表明，可及染色质图谱中的动态与发育过程中的时间转录相匹配。对阶段特异性ATAC-seq位点的基序分析预测了多种ApiAP2转录因子的体内结合位点和功能。最后，一些克隆性变异基因(CVG)的不同表达状态，包括EBA、PHIST、var和CLAG基因，与其启动子处的不同ATAC-seq信号有关。总之，这项研究确定了基因组范围的调节区可能在恶性疟原虫的发育转变和CVG表达中发挥重要功能。
Human malaria is a devastating disease and a major cause of poverty in resource-limited countries. To develop and adapt within hosts Plasmodium falciparum undergoes drastic switches in gene expression. To identify regulatory regions in the parasite genome, we performed genome-wide profiling of chromatin accessibility in two culture-adapted isogenic subclones at four developmental stages during the intraerythrocytic cycle by using the Assay for Transposase-Accessible Chromatin by sequencing (ATAC-seq). Tn5 transposase hypersensitivity sites (THSSs) localize preferentially at transcriptional start sites (TSSs). Chromatin accessibility by ATAC-seq is predictive of active transcription and of the levels of histone marks H3K9ac and H3K4me3. Our assay allows the identification of novel regulatory regions including TSS and enhancer-like elements. We show that the dynamics in the accessible chromatin profile matches temporal transcription during development. Motif analysis of stage-specific ATAC-seq sites predicts the in vivo binding sites and function of multiple ApiAP2 transcription factors. At last, the alternative expression states of some clonally variant genes (CVGs), including eba, phist, var and clag genes, associate with a differential ATAC-seq signal at their promoters. Altogether, this study identifies genome-wide regulatory regions likely to play an essential function in the developmental transitions and in CVG expression in P. falciparum.
登录
查看更多内容
影响因子：
4.4
作者：
Broadbent KM;Broadbent JC;Ribacke U;Wirth D;Rinn JL;Sabeti PC
通讯作者：
Sabeti PC
影响因子：
9.8
作者：
Bozdech, Zbynek;Llinas, Manuel;Pulliam, Brian Lee;Wong, Edith D;Zhu, Jingchun;DeRisi, Joseph L
通讯作者：
DeRisi, Joseph L
影响因子：
6.7
作者：
Cortés A;Carret C;Kaneko O;Yim Lim BY;Ivens A;Holder AA
通讯作者：
Holder AA
影响因子：
6.7
作者：
Campbell TL;De Silva EK;Olszewski KL;Elemento O;Llinás M
通讯作者：
Llinás M
影响因子：
14.9
作者：
Balaji S;Babu MM;Iyer LM;Aravind L
通讯作者：
Aravind L