The Mechanism On Regulation Of Human C-Reactive Protein Expression By APEX1

C-reactive protein(C-reactive protein,CRP)is a very old class of proteins that occurs in higher animals earlier than the complement system and the acquired immune system.CRP can be used as a pattern recognition receptor.The normal physiological level of plasma CRP content is 0.8ug/ml,Under stimulation conditions,it can rapidly rise to 5ug/ml within 6 hours,and then come to a peak of 1000ug/ml after 48 h.CRP responds to interleukins 6(Interleukin-6,IL-6)and interleukin 1β(Interleukin-1β,IL-1β)combined stimulation that can produce an acute phase typically.Previous studies have shown that the rs3091244 locus in the promoter region of CRP gene has high frequency mutations in various tumor tissues.This subject is based on the putative biological function to give priority to the SNP(Nucleotide Polymorphism Site,SNP)in CRP,and our laboratory previous studies has shown that the dynamic methylation of the promoter region is also involved in regulation in CRP expression.Therefore,rs3091244 act as a CpG-SNP must have a unique regulatory mechanism.First,rs3091244 was identified as a CRP expression quantitative trait locus(eQTL)in the healthy population,and its A allele has a higher mRNA expression level.Then,using the probes with different positions of rs3091244,it was found that APEX1(Apurinic/Apyrimidinic Endodeoxyribonuclease 1,APEX1)may participate in CRP expression and the APEX1 was found to act as a negative regulator in this process.The transcription factor usually binds to the enhancer or promoter region on the adjacent DNA of the regulated gene domain.These experiments indicated that the C of the rs3091244 is more AP-binding than the T allele,and this fact is confirmed by several binding expeiments including some vitro experiments and cell binding experiments.Demonstration in this subject also proves that the transcription factor activity domain of APEX1 is independent of the functional domain that acts as a DNA repair enzyme.All in all,this study identified a novel regulator of CRP expression,revealing that this regulator is biased at the SNP site due to base steric hindrance,some biological processes exploxed in ChIP-seq which revealed that APEX1 is involved as a transcription factor and interacts with other protein.The degree of association between APEX1 and CRP promoter region methylation was investigated initially.