Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York.
Exp Dermatol. 2019 Apr;28(4):453-463. doi: 10.1111/exd.13872. Epub 2019 Feb 12.
Cell-type- and cell-state-specific patterns of covalent modifications on DNA and histone tails form global epigenetic profiles that enable spatiotemporal regulation of gene expression. These epigenetic profiles arise from coordinated activities of transcription factors and epigenetic modifiers, which result in cell-type-specific outputs in response to dynamic environmental conditions and signalling pathways. Recent mouse genetic and functional studies have highlighted the physiological significance of global DNA and histone epigenetic modifications in skin. Importantly, specific epigenetic profiles are emerging for adult skin stem cells that are associated with their cell fate plasticity and proper activity in tissue regeneration. We can now begin to draw a more comprehensive picture of how epigenetic modifiers orchestrate their cell-intrinsic role with microenvironmental cues for proper skin development, homeostasis and wound repair. The field is ripe to begin to implement these findings from the laboratory into skin therapies.
DNA 和组蛋白尾部上的共价修饰的细胞类型和细胞状态特异性模式形成了全局表观遗传特征，从而实现了基因表达的时空调控。这些表观遗传特征源自转录因子和表观遗传修饰物的协调活动，这些活动导致细胞类型特异性输出，以响应动态环境条件和信号通路。最近的小鼠遗传和功能研究强调了皮肤中全局 DNA 和组蛋白表观遗传修饰的生理意义。重要的是，正在出现与成体皮肤干细胞的细胞命运可塑性和组织再生中的适当活性相关的特定表观遗传特征。我们现在可以开始更全面地了解表观遗传修饰物如何与微环境线索一起协调其内在的细胞作用，以实现皮肤的正常发育、稳态和伤口修复。该领域已经成熟，可以将这些实验室发现应用于皮肤治疗中。
