Genome-wide landscape of ApiAP2 transcription factors reveals a heterochromatin-associated regulatory network during Plasmodium falciparum blood-stage development.
Genome-wide landscape of ApiAP2 transcription factors reveals a heterochromatin-associated regulatory network during Plasmodium falciparum blood-stage development.
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DOI：
10.1093/nar/gkac176
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发表时间：
2022-04-08
影响因子：
14.9
通讯作者：
Zhang Q
中科院分区：
文献类型：
--
作者：
Shang X;Wang C;Fan Y;Guo G;Wang F;Zhao Y;Sheng F;Tang J;He X;Yu X;Zhang M;Zhu G;Yin S;Mu J;Culleton R;Cao J;Jiang M;Zhang Q
异染色质相关基因沉默控制疟疾寄生虫中的多种生理过程，然而，人们对参与异染色质组织的调控网络和顺式作用序列以及它们如何调节异染色质基因表达知之甚少。基于通过 ChIP-seq 分析对 18 个 Apicomplexan AP2 转录因子的全基因组占有率进行系统分析，我们鉴定并表征了 8 个异染色质相关因子 (PfAP2-HF)，它们在异染色质区域内表现出优先富集，但具有差异覆盖特征。尽管这些 ApiAP2 通过特定的 DNA 基序靶向常染色质基因位点，但它们可能是独立于 DNA 基序识别的异染色质的组成部分。 ApiAP2 因子的系统敲除筛选与 RNA-seq 转录组分析相结合，揭示了异染色质基因表达的三种激活剂和三种抑制剂，包括四种 PfAP2-HF。值得注意的是，PfAP2-HC 耗尽后，毒力基因的表达要么完全沉默，要么显着降低。综合多组学分析揭示，除了转录控制中局部染色质结构和 ApiAP2 之间发生动态相互作用外，自动调节和前馈循环是 ApiAP2 调节网络的共同特征。总的来说，这项研究提供了宝贵的资源，描述了 ApiAP2 家族的全基因组景观，并深入了解了疟原虫血液阶段发育过程中该家族内部的功能分歧和合作。
Heterochromatin-associated gene silencing controls multiple physiological processes in malaria parasites, however, little is known concerning the regulatory network and cis-acting sequences involved in the organization of heterochromatin and how they modulate heterochromatic gene expression. Based on systematic profiling of genome-wide occupancy of eighteen Apicomplexan AP2 transcription factors by ChIP-seq analysis, we identify and characterize eight heterochromatin-associated factors (PfAP2-HFs), which exhibit preferential enrichment within heterochromatic regions but with differential coverage profiles. Although these ApiAP2s target euchromatic gene loci via specific DNA motifs, they are likely integral components of heterochromatin independent of DNA motif recognition. Systematic knockout screenings of ApiAP2 factors coupled with RNA-seq transcriptomic profiling revealed three activators and three repressors of heterochromatic gene expression including four PfAP2-HFs. Notably, expression of virulence genes is either completely silenced or significantly reduced upon the depletion of PfAP2-HC. Integrated multi-omics analyses reveal autoregulation and feed-forward loops to be common features of the ApiAP2 regulatory network, in addition to the occurrence of dynamic interplay between local chromatin structure and ApiAP2s in transcriptional control. Collectively, this study provides a valuable resource describing the genome-wide landscape of the ApiAP2 family and insights into functional divergence and cooperation within this family during the blood-stage development of malaria parasites.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
9.6
作者：
Batugedara G;Lu XM;Bunnik EM;Le Roch KG
通讯作者：
Le Roch KG
DOI：
10.1093/bioinformatics/btv562
发表时间：
2016-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Gel B;Díez-Villanueva A;Serra E;Buschbeck M;Peinado MA;Malinverni R
通讯作者：
Malinverni R
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：
64.8
作者：
Freitas-Junior, LH;Bottius, E;Scherf, A
通讯作者：
Scherf, A