دورية أكاديمية

Actin-related protein Arp4 regulates euchromatic gene expression and development through H2A.Z deposition in blood-stage Plasmodium falciparum

التفاصيل البيبلوغرافية
العنوان: Actin-related protein Arp4 regulates euchromatic gene expression and development through H2A.Z deposition in blood-stage Plasmodium falciparum
المؤلفون: Hui Liu, Xin-Yu Cui, Dan-Dan Xu, Fei Wang, Lin-Wen Meng, Yue-Meng Zhao, Meng Liu, Shi-Jun Shen, Xiao-Hui He, Qiang Fang, Zhi-Yong Tao, Ci-Zong Jiang, Qing-Feng Zhang, Liang Gu, Hui Xia
المصدر: Parasites & Vectors, Vol 13, Iss 1, Pp 1-15 (2020)
بيانات النشر: BMC, 2020.
سنة النشر: 2020
المجموعة: LCC:Infectious and parasitic diseases
مصطلحات موضوعية: Malaria, Plasmodium falciparum, Arp4, Chromatin structure, Gene regulation, Infectious and parasitic diseases, RC109-216
الوصف: Abstract Background Malaria caused by Plasmodium spp. is still a major threat to public health globally. The various approaches to developing new antimalarial agents rely on the understanding of the complex regulatory mechanisms of dynamic gene expression in the life-cycle of these malaria parasites. The nuclear members of the evolutionarily conserved actin-related protein nuclear (ARP) superfamily are the major components of nucleosome remodelling complexes. In the human malaria parasite Plasmodium falciparum, bioinformatics analysis has predicted three ARP orthologues: PfArp1, PfArp4 and PfArp6. However, little is known about the biological functions of putative PfArp4. In this study, we aimed to investigate the function and the underlying mechanisms of PfArp4 gene regulation. Methods A conditional gene knockdown approach was adopted by incorporating the glucosamine-inducible glmS ribozyme sequence into the 3’ UTR of the PfArp4 and PfArp6 genes. The transgenic parasites PfArp4-Ty1-Ribo, PfArp6-Ty1-Ribo and pL6-PfArp4-Ty1::PfArp6-HA were generated by the CRISPR-Cas9 technique. The knockdown effect in the transgenic parasite was measured by growth curve assay and western blot (WB) analysis. The direct interaction between PfArp4 and PfArp6 was validated by co-IFA and co-IP assays. The euchromatic gene expression mediated through H2A.Z (histone H2A variant) deposition and H3K9ac modification at promoters and regulated by PfArp4, was determined by RNA-seq and ChIP-seq. Results The inducible knockdown of PfArp4 inhibited blood-stage development of P. falciparum. PfArp4 and PfArp6 were colocalized in the nucleus of P. falciparum parasites. PfArp4 gene knockdown altered the global transcriptome. PfArp4 protein colocalized with the histone variant H2A.Z and euchromatic marker H3K9ac in intergenic regions. The inducible downregulation of PfArp4 resulted in the depletion of H2A.Z and lower H3K9ac levels at the upstream regions of eukaryotic genes, thereby repressing the transcriptional abundance of H2A.Z-dependent genes. Conclusions Our findings suggest that PfArp4 regulates the cell cycle by controlling H2A.Z deposition and affecting centromere function, contributing to the understanding the complex epigenetic regulation of gene expression and the development of P. falciparum.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1756-3305
Relation: http://link.springer.com/article/10.1186/s13071-020-04139-6; https://doaj.org/toc/1756-3305
DOI: 10.1186/s13071-020-04139-6
URL الوصول: https://doaj.org/article/90b8f3fd106e44158c8335eaf481c553
رقم الأكسشن: edsdoj.90b8f3fd106e44158c8335eaf481c553
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:17563305
DOI:10.1186/s13071-020-04139-6