急性期蛋白是一类在炎症反应中浓度发生剧烈变化的血浆蛋白，在宿主防御和炎症调节中发挥着重要作用。对以C-反应蛋白（C-reactive protein, CRP）为代表的急性期蛋白表达调节的理解，主要集中于转录因子到近端启动子的募集。DNA甲基化是基因表达静默的重要表观遗传学机制，多发生于CpG基序内。虽然大部分哺乳动物基因启动子处于不易甲基化的CpG岛中，但CRP启动子内CpG密度很低。有意思的是，这些CpG或位于关键转录因子结合序列中，或包含显著影响CRP表达的单核苷酸多态性位点，暗示DNA甲基化对CRP表达的重要影响。与此相符，我们的系列预实验亦提示CRP的表达由其启动子的原位甲基化动态可逆调节。由于低CpG密度也是其他急性期蛋白启动子的共同特征，本项目提出“启动子甲基化动态决定急性期蛋白的表达模式”，并将围绕此展开深入研究，阐明其分子机制，为以急性期蛋白表达为标靶的治疗提供新的思路。

Acute phase proteins (APPs) are a class of secretory proteins whose blood concentrations undergo large changes in inflammation. Current understanding of the expression regulation of APPs, among which C-reactive protein (CRP) is a representative, is mainly on proximal promoter binding of transcription factors. DNA methylation occurs primarily in CpG motif, and represents a major epigenetic mechanism of gene silencing. Although promoters of most mammalian genes are in CpG islands with little methylation, the promoter of CRP only contains 5 CpG motifs. These CpG motifs either locates in the binding sites of key transcription factors, or harbors the single nucleotide polymorphism (SNP) site that has a marked impact on expression but stays outside the identified regulatory sequences. These imply that CRP expression might be regulated by promoter methylation. Our preliminary results indeed revealed the dependence of CRP expression on the reversible methylation of its promoter. Because the promoters of other APPs also exhibit similarly low CpG densities, this project thus proposes that the expression pattern of APPs is determined by promoter methylation dynamics and will investigate the underlying molecular mechanisms, a comprehensive understanding of which might also lead to new therapy by targeting APP expression.