The skin is the largest organ of the human body. Upon injury, the skin triggers a sequence of signaling pathways that induce epithelial proliferation, migration, and ultimately, the re-establishment of the epithelial barrier. Our study explores the unknown epigenetic regulations of wound healing from a histone perspective. Posttranslational modifications of histones enhance chromatin accessibility and modify gene transcription. Full-thickness wounds were made in the dorsal skin of twenty-four C57/B6 mice (C57BL/6J), followed by the use of ring-shaped silicone splints to prevent wound contraction. Tissue samples were collected at three time points (post-operatory day 1, 4, and 9), and processed for histology. Immunofluorescence was performed in all-time points using markers for histone H4 acetylation at lysines K5, K8, K12, and K16. We found well-defined histone modifications associated with the stages of healing. Most exciting, we showed that the epidermis located at a distance from the wound demonstrated changes in histone acetylation, particularly the deacetylation of histone H4K5, H4K8, and H4K16, and hyperacetylation of H4K12. The epidermis adjacent to the wound revealed the deacetylation of H4K5 and H4K8 and hyperacetylation of H4K12. Conversely, the migratory epithelium (epithelial tongue) displayed significant acetylation of H4K5 and H4K12. The H4K5 and H4K8 were decreased in the newly formed epidermis, which continued to display high levels of H4K12 and H4K16. This study profiles the changes in histone H4 acetylation in response to injury. In addition to the epigenetic changes found in the healing tissue, these changes also took place in tissues adjacent and distant to the wound. Furthermore, not only deacetylation but also hyperacetylation occurred during tissue repair and regeneration.

中文翻译：

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皮肤伤口愈合可触发组蛋白H4的表观遗传修饰。

皮肤是人体最大的器官。受伤后，皮肤会触发一系列信号通路，这些信号通路会诱导上皮细胞增殖，迁移，最终导致上皮屏障的重建。我们的研究从组蛋白的角度探讨了伤口愈合的未知表观遗传规律。组蛋白的翻译后修饰增强了染色质的可及性并修饰了基因转录。在二十四只C57 / B6小鼠（C57BL / 6J）的背部皮肤中制成全层伤口，然后使用环形硅胶夹板防止伤口收缩。在三个时间点（术后第1、4和9天）收集组织样本，并进行组织学处理。使用赖氨酸K5，K8，K12和K16处组蛋白H4乙酰化的标记物在所有时间点进行免疫荧光。我们发现与治愈阶段相关的定义明确的组蛋白修饰。最令人兴奋的是，我们表明距伤口一定距离的表皮表现出组蛋白乙酰化的变化，尤其是组蛋白H4K5，H4K8和H4K16的脱乙酰化以及H4K12的超乙酰化。伤口附近的表皮显示出H4K5和H4K8的脱乙酰基和H4K12的超乙酰基。相反，迁移的上皮（上皮舌）显示出H4K5和H4K12的显着乙酰化。H4K5和H4K8在新形成的表皮中减少，继续显示高水平的H4K12和H4K16。这项研究概述了响应损伤的组蛋白H4乙酰化的变化。除了在愈合组织中发现表观遗传变化外，这些变化也发生在伤口附近和远处的组织中。此外，在组织修复和再生期间不仅发生了脱乙酰作用，而且发生了超乙酰化作用。