Epigenetic editing by CRISPR/dCas9 in Plasmodium falciparum

doi:10.1073/pnas.1813542116

	Epigenetic editing by CRISPR/dCas9 in Plasmodium falciparum
	Xiao, Bo 1; Yin, Shigang 1; Hu, Yang 1; Sun, Maoxin1,2 ; Wei, Jieqiong 1; Huang, Zhenghui 1; Wen, Yuhao 1; Dai, Xueyu 1; Chen, Huiling 1; Mu, Jianbing 3; Cui, Liwang 4; Jiang, Lubin1,2
	2019-01-02
发表期刊	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (IF:9.4[JCR-2023],10.8[5-Year])
ISSN	0027-8424
卷号	116 期号:1 页码:255-260
发表状态	已发表
DOI	10.1073/pnas.1813542116
摘要	Genetic manipulation remains a major obstacle for understanding the functional genomics of the deadliest malaria parasite Plasmodium falciparum. Although the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeat/CRISPR-associated protein 9) system has been successfully applied to introduce permanent changes in the parasite genome, its use is still limited. Here we show that fusing different epigenetic effector domains to a Cas9 null mutant efficiently and specifically reprograms the expression of target genes in P. falciparum. By precisely writing and erasing histone acetylation at the transcription start site regions of the invasion-related genes reticulocyte binding protein homolog 4 (rh4) and erythrocyte binding protein 175 (eba-175), respectively, we achieved significant activation of rh4 and repression of eba175, leading to the switch of the parasite invasion pathways into human erythrocytes. By using the epigenetic knockdown system, we have also characterized the effects of PfSET1, previously identified as an essential gene, on expression of mainly trophozoite- and schizont-specific genes, and therefore regulation of the growth of the mature forms of P. falciparum. This epigenetic CRISPR/dCas9 system provides a powerful approach for regulating gene expression at the transcriptional level in P. falciparum.
关键词	malaria parasite CRISPR/dCas9 epigenetic editing invasion change
收录类别	SCI ; SCIE
语种	英语
资助项目	National Institute of Allergy and Infectious Diseases[R01AI116466] ; National Institute of Allergy and Infectious Diseases[U19AI089672]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000454707700041
出版者	NATL ACAD SCIENCES
WOS关键词	INVASION ; ACETYLTRANSFERASE ; TRANSFORMATION ; INTEGRATION ; EXPRESSION ; RECEPTOR ; PROTEIN ; GENES
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/30058
专题	生命科学与技术学院_博士生生命科学与技术学院_特聘教授组_江陆斌组
通讯作者	Jiang, Lubin
作者单位	1.Chinese Acad Sci, Univ Chinese Acad Sci, Unit Human Parasite Mol & Cell Biol, Key Lab Mol Virol & Immunol,Inst Pasteur Shanghai, Shanghai 200031, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 3.NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA 4.Univ S Florida, Morsani Coll Med, Dept Internal Med, Tampa, FL 33612 USA
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Xiao, Bo,Yin, Shigang,Hu, Yang,et al. Epigenetic editing by CRISPR/dCas9 in Plasmodium falciparum[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2019,116(1):255-260.
APA	Xiao, Bo.,Yin, Shigang.,Hu, Yang.,Sun, Maoxin.,Wei, Jieqiong.,...&Jiang, Lubin.(2019).Epigenetic editing by CRISPR/dCas9 in Plasmodium falciparum.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,116(1),255-260.
MLA	Xiao, Bo,et al."Epigenetic editing by CRISPR/dCas9 in Plasmodium falciparum".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 116.1(2019):255-260.