DNA helicase RecQ1 regulates mutually exclusive expression of virulence genes in Plasmodium falciparum via heterochromatin alteration

doi:10.1073/pnas.1811766116

	DNA helicase RecQ1 regulates mutually exclusive expression of virulence genes in Plasmodium falciparum via heterochromatin alteration
	Li, Zhou 1; Yin, Shigang 1; Sun, Maoxin1,2 ; Cheng, Xiu 1; Wei, Jieqiong 1; Gilbert, Nicolas 1,4; Miao, Jun 3; Cui, Liwang 3; Huang, Zhenghui 1; Dai, Xueyu 1; Jiang, Lubin1,2
	2019-02-19
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:8 页码:3177-3182
发表状态	已发表
DOI	10.1073/pnas.1811766116
摘要	The Plasmodium falciparum var gene family encodes similar to 60 surface antigens by which parasites escape the host immune responses via clonal expression of var genes. However, the mechanism controlling this mutual exclusivity, associated with alterations in chromatin assembly, is not understood. Here, we determined how expression of the var gene family is regulated by two RecQ DNA helicase family members, PfRecQ1 and PfWRN, in P. falciparum. Through genetic manipulation, we found that the complete var repertoire was silenced on PfRecQ1 knockout, whereas their expression did not show noticeable changes when PfWRN was knocked out. More important, mutually exclusive expression of var genes could be rescued by complementation of PfRecQ1. In addition, knocking out either of these two helicase genes changed the perinuclear cluster distribution of subtelomeres and subtelomeric var genes. Whereas deletion of PfRecQ1 increased the heterochromatin mark trimethylated (H3K9me3) at the transcription start site (TSS) of the var gene upsC1, that deletion had no effect on the global distribution of H3K9me3 over gene bodies, including those for the var genes. ChIP-seq assay showed that PfRecQ1 was enriched globally at the TSSs of all genes, whereas PfWRN-enriched regions occurred at the gene bodies of the var gene family, but not of other genes or at TSSs of all genes. On PfRecQ1 deletion, the upsC1 var gene moved from the active perinuclear transcription region to a silenced region of the upsC type. These findings imply that PfRecQ1, but not PfWRN, is essential for maintaining the clonal expression of var genes.
关键词	DNA helicases heterochromatin virulence gene mutually exclusive expression Plasmodium falciparum
收录类别	SCI ; SCIE
语种	英语
资助项目	National Institute of Allergy and Infectious Diseases of the National Institutes of Health[R01AI116466] ; National Institute of Allergy and Infectious Diseases of the National Institutes of Health[U19AI089672]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000459074400059
出版者	NATL ACAD SCIENCES
WOS关键词	ANTIGENIC VARIATION ; GENOME ; MALARIA ; WERNER
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/30405
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	Huang, Zhenghui; Dai, Xueyu; Jiang, Lubin
作者单位	1.Univ Chinese Acad Sci, 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.Univ S Florida, Morsani Coll Med, Dept Internal Med, Tampa, FL 33612 USA 4.CHU Montpellier, INSERM U1183, Inst Med Regeneratrice & Biotherapie, Montpellier, France
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Li, Zhou,Yin, Shigang,Sun, Maoxin,et al. DNA helicase RecQ1 regulates mutually exclusive expression of virulence genes in Plasmodium falciparum via heterochromatin alteration[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2019,116(8):3177-3182.
APA	Li, Zhou.,Yin, Shigang.,Sun, Maoxin.,Cheng, Xiu.,Wei, Jieqiong.,...&Jiang, Lubin.(2019).DNA helicase RecQ1 regulates mutually exclusive expression of virulence genes in Plasmodium falciparum via heterochromatin alteration.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,116(8),3177-3182.
MLA	Li, Zhou,et al."DNA helicase RecQ1 regulates mutually exclusive expression of virulence genes in Plasmodium falciparum via heterochromatin alteration".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 116.8(2019):3177-3182.