Arias-Pérez Osvaldo, Escobedo-Tapia Thelma, Cintora-Ahumada Cecilia, León-Solís Lizbel, Leyva-García Norberto, Aréchaga-Ocampo Elena, Franco-Cendejas Rafael, Hernández-Hernández Oscar, Suárez-Sánchez Rocío
Laboratorio de Medicina Genómica, Departamento de Genética, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", Mexico City 14389, Mexico.
Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana-Unidad Cuajimalpa, Mexico City 05348, Mexico.
Life (Basel). 2024 Dec 1;14(12):1581. doi: 10.3390/life14121581.
Severe burns activate systemic inflammation and lead to an increase in cytokine levels. Epigenetic elements are key regulators of inflammation; however, their involvement in severe burns has not been studied. In this work, we aimed to unveil the histone H3 posttranslational modifications (PTM) profile and their enrichment in promoters of inflammatory genes in response to severe burns.
The levels of H3 PTMs were analyzed by ELISA assays in circulating cells from burn patients. ChIP assays were conducted to evaluate the enrichment of H3K9me2 and H3S28p at the promoter of CXCL8, IL-17, TNFA, IL-6, FOS, and IL-1B genes.
We found that eight H3 PTMs decreased at 5 days post-burn. Burn patients showed a decreased enrichment of H3K9me2 in CXCL8, IL-17, and TNFA promoters, whereas IL-6, FOS, and IL-1B promoters displayed an H3S28p enrichment diminution during the first 10 days post-burn. Interestingly, burn-injured septic patients exhibited an increased enrichment of H3K9me2 in TNFA, IL-1B, CXCL8, and IL-17 promoters, whereas H3S28p was increased in promoters of TNFA and IL-1B at 1 dpb.
Severe burns trigger epigenetic changes and differential H3 PTM enrichment at inflammation gene promoters. Epigenetic misregulation of H3 may be involved in sepsis occurrence after severe burn injury.
严重烧伤会激活全身炎症反应并导致细胞因子水平升高。表观遗传元件是炎症的关键调节因子；然而，它们在严重烧伤中的作用尚未得到研究。在本研究中，我们旨在揭示组蛋白H3翻译后修饰（PTM）谱及其在严重烧伤后炎症基因启动子中的富集情况。
通过ELISA分析烧伤患者循环细胞中H3 PTM的水平。进行染色质免疫沉淀（ChIP）分析以评估H3K9me2和H3S28p在CXCL8、IL-17、TNFA、IL-6、FOS和IL-1B基因启动子处的富集情况。
我们发现烧伤后5天，8种H3 PTM水平下降。烧伤患者CXCL8、IL-17和TNFA启动子中H3K9me2的富集减少，而在烧伤后的前10天，IL-6、FOS和IL-1B启动子中H3S28p的富集减少。有趣的是，烧伤合并脓毒症患者TNFA、IL-1B、CXCL8和IL-17启动子中H3K9me2的富集增加，而在烧伤后1天，TNFA和IL-1B启动子中H3S28p增加。
严重烧伤会引发表观遗传变化以及炎症基因启动子处H3 PTM的差异富集。H3的表观遗传失调可能参与严重烧伤后脓毒症的发生。
