scholarly journals DNA methylation directly downregulates human cathelicidin antimicrobial peptide gene (CAMP) promoter activity

Oncotarget ◽  
2017 ◽  
Vol 8 (17) ◽  
pp. 27943-27952 ◽  
Author(s):  
Xi Chen ◽  
Guangying Qi ◽  
Mingqun Qin ◽  
Yantao Zou ◽  
Kanghua Zhong ◽  
...  
Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 853
Author(s):  
Siti Aisyah Faten Mohamed Sa’dom ◽  
Sweta Raikundalia ◽  
Shaharum Shamsuddin ◽  
Wei Cun See Too ◽  
Ling Ling Few

Choline kinase (CK) is the enzyme catalyzing the first reaction in CDP-choline pathway for the biosynthesis of phosphatidylcholine. Higher expression of the α isozyme of CK has been implicated in carcinogenesis, and inhibition or downregulation of CKα (CHKA) is a promising anticancer approach. This study aimed to investigate the regulation of CKα expression by DNA methylation of the CpG islands found on the promoter of this gene in MCF-7 cells. Four CpG islands have been predicted in the 2000 bp promoter region of ckα (chka) gene. Six CpG island deletion mutants were constructed using PCR site-directed mutagenesis method and cloned into pGL4.10 vectors for promoter activity assays. Deletion of CpG4C region located between –225 and –56 significantly increased the promoter activity by 4-fold, indicating the presence of important repressive transcription factor binding site. The promoter activity of methylated full-length promoter was significantly lower than the methylated CpG4C deletion mutant by 16-fold. The results show that DNA methylation of CpG4C promotes the binding of the transcription factor that suppresses the promoter activity. Electrophoretic mobility shift assay analysis showed that cytosine methylation at MZF1 binding site in CpG4C increased the binding of putative MZF1 in nuclear extract. In conclusion, the results suggest that DNA methylation decreased the promoter activity by promoting the binding of putative MZF1 transcription factor at CpG4C region of the ckα gene promoter.


2021 ◽  
Author(s):  
Zie Wang ◽  
Jie Deng ◽  
Tingting Liang ◽  
Linlin Su ◽  
Lilei Zheng ◽  
...  

Abstract Background: WRKY transcription factors (TFs) play vital roles in plant growth and development, secondary metabolite synthesis, and response to biotic and abiotic stresses. In a previous transcriptome sequencing analysis of Lilium regale Wilson, we identified multiple WRKY TFs that respond to exogenous methyl jasmonate treatment and lily Fusarium wilt (Fusarium oxysporum).Results: In the present study, the WRKY TF LrWRKY3 was further analyzed to reveal its function in defense response to F. oxysporum. The LrWRKY3 protein was localized in the plant cell nucleus, and LrWRKY3 transgenic tobacco lines showed higher resistance to F. oxysporum compared with wild-type (WT) tobacco. In addition, some genes related to jasmonic acid (JA) biosynthesis, salicylic acid (SA) signal transduction, and disease resistance had higher transcriptional levels in the LrWRKY3 transgenic tobacco lines than in the WT. On the contrary, L. regale scales transiently expressing LrWRKY3 RNA interference fragments showed higher sensitivity to F. oxysporum infection. Moreover, a F. oxysporum-induced defensin gene, Def1, was isolated from L. regale, and the recombinant protein LrDef1 isolated and purified from Escherichia coli possessed antifungal activity to several phytopathogens, including F. oxysporum. Furthermore, co-expression of LrWRKY3 and the LrDef1 promoter in tobacco evidently up-regulated the expression activity of the LrDef1 promoter.Conclusions: These results clearly indicate that LrWRKY3 is an important positive regulator in response to F. oxysporum infection, and one of its targets is the antimicrobial peptide gene LrDef1.


2003 ◽  
Vol 23 (22) ◽  
pp. 8272-8281 ◽  
Author(s):  
Hanna Uvell ◽  
Ylva Engström

ABSTRACT Innate immune reactions are crucial processes of metazoans to protect the organism against overgrowth of faster replicating microorganisms. Drosophila melanogaster is a precious model for genetic and molecular studies of the innate immune system. In response to infection, the concerted action of a battery of antimicrobial peptides ensures efficient killing of the microbes. The induced gene expression relies on translocation of the Drosophila Rel transcription factors Relish, Dif, and Dorsal to the nucleus where they bind to κB-like motifs in the promoters of the inducible genes. We have identified another putative promoter element, called region 1 (R1), in a number of antimicrobial peptide genes. Site-directed mutagenesis of the R1 site diminished Cecropin A1 (CecA1) expression in transgenic Drosophila larvae and flies. Infection of flies induced a nuclear R1-binding activity that was unrelated to the κB-binding activity in the same extracts. Although the R1 motif was required for Rel protein-mediated CecA1 expression in cotransfection experiments, our data argue against it being a direct target for the Drosophila Rel proteins. We propose that the R1 and κB motifs are targets for distinct regulatory complexes that act in concert to promote high levels of antimicrobial peptide gene expression in response to infection.


2005 ◽  
Vol 56 (416) ◽  
pp. 1685-1695 ◽  
Author(s):  
Dmytro P. Yevtushenko ◽  
Rafael Romero ◽  
Benjamin S. Forward ◽  
Robert E. Hancock ◽  
William W. Kay ◽  
...  

2019 ◽  
Vol 29 (4) ◽  
pp. 554-563 ◽  
Author(s):  
Dominik Hartl ◽  
Arnaud R. Krebs ◽  
Ralph S. Grand ◽  
Tuncay Baubec ◽  
Luke Isbel ◽  
...  

2021 ◽  
Vol 88 ◽  
pp. 108543
Author(s):  
Babajide A. Ojo ◽  
Peiran Lu ◽  
Sanmi E. Alake ◽  
Bryant Keirns ◽  
Kendall Anderson ◽  
...  

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Yong-Zhen Huang ◽  
Liang-Zhi Zhang ◽  
Xin-Sheng Lai ◽  
Ming-Xun Li ◽  
Yu-Jia Sun ◽  
...  

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