Pegoraro Silvia, Balduit Andrea, Mangogna Alessandro, Kishore Uday, Ricci Giuseppe, Agostinis Chiara, Bulla Roberta
Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, ;Italy.
Department of Veterinary Medicine, United Arab Emirates (U.E.A.) University, Al Ain, ;United Arab Emirates.
Front Immunol. 2024 Dec 3;15:1498097. doi: 10.3389/fimmu.2024.1498097. eCollection 2024.
Human C1q is a multifaceted complement protein whose functions range from activating the complement classical pathway to immunomodulation and promoting placental development and tumorigenesis. It is encoded by the , , and genes located on chromosome 1. C1q, unlike most complement components, has extrahepatic expression by a range of cells including macrophages, monocytes and immature dendritic cells. Its local synthesis under the conditions of inflammation and for the purpose of removal of altered self requires its strict transcriptional regulation. To delve into transcriptional regulation and unravel potential epigenetic influences, we conducted an analysis utilizing a range of online tools and datasets. Co-expression analysis revealed tight coordination between , , and genes. Strikingly, distinct epigenetic patterns emerged across various cell types expressing or lacking these genes, with unique histone marks and DNA methylation status characterizing their regulatory landscape. Notably, the investigation extended to tumor contexts, unveiled potential epigenetic roles in malignancies. The cell type and tumor-specific histone modifications and chromatin accessibility patterns underscore the dynamic nature of epigenetic regulation of , providing crucial insights into the intricate mechanisms governing the expression of these immunologically significant genes. The findings provide a foundation for future investigations into targeted epigenetic modulation, offering insights into potential therapeutic avenues for immune-related disorders and cancer mediated via C1q.
人C1q是一种多面补体蛋白,其功能范围从激活补体经典途径到免疫调节以及促进胎盘发育和肿瘤发生。它由位于1号染色体上的C1QA、C1QB和C1QC基因编码。与大多数补体成分不同,C1q在包括巨噬细胞、单核细胞和未成熟树突状细胞在内的一系列细胞中具有肝外表达。在炎症条件下以及为了清除改变的自身而进行的局部合成需要其严格的转录调控。为了深入研究转录调控并揭示潜在的表观遗传影响,我们利用一系列在线工具和数据集进行了一项分析。共表达分析揭示了C1QA、C1QB和C1QC基因之间的紧密协调。引人注目的是,在表达或缺乏这些基因的各种细胞类型中出现了不同的表观遗传模式,独特的组蛋白标记和DNA甲基化状态表征了它们的调控格局。值得注意的是,该研究扩展到肿瘤背景,揭示了表观遗传在恶性肿瘤中的潜在作用。细胞类型和肿瘤特异性组蛋白修饰以及染色质可及性模式强调了C1q表观遗传调控的动态性质,为控制这些免疫重要基因表达的复杂机制提供了关键见解。这些发现为未来靶向表观遗传调节的研究奠定了基础,为通过C1q介导的免疫相关疾病和癌症的潜在治疗途径提供了见解。