Post-translational modifications on nucleosomal histones represent a key epigenetic regulatory mechanism to mediate the complex gene expression, DNA replication, and cell cycle changes that occur in embryonic cells undergoing lineage specification, maturation, and differentiation during development. Here, we investigated the dynamics of 13 key histone marks in epidermal cells at three distinct stages of embryonic skin development and identified significant changes that corresponded with the maturation of the proliferative basal epidermal cells and terminally differentiated cells in the stratified layers. In particular, H3K4me3 and H3K27ac were accumulated and became more prominent in the basal cells at later stages of epidermal development, while H3K27me3 was found to be low in the basal cells but highly enriched in the differentiated suprabasal cell types. Constitutive heterochromatin marked by H4K20me3 was also significantly elevated in differentiated epidermal cells at late gestation stages, which exhibited a concomitant loss of H4K16 acetylation. These differential chromatin profiles were established in the embryonic skin by gestation day 15 and further amplified at E18 and in postnatal skin. Our results reveal the dynamic chromatin states that occur as epidermal progenitor cells commit to the lineage and differentiate into the different cells of the stratified epidermis and provide insight to the underlying epigenetic pathways that support normal epidermal development and homoeostasis.

核小体组蛋白的翻译后修饰代表了关键的表观遗传调控机制，可介导复杂基因表达，DNA复制和发育过程中经历谱系指定，成熟和分化的胚胎细胞中发生的细胞周期变化。在这里，我们调查了胚胎皮肤发育三个不同阶段表皮细胞中13个关键组蛋白标记的动力学，并确定了与分层的基础基底表皮细胞和终末分化细胞成熟相对应的显着变化。特别是在表皮发育的后期，H3K4me3和H3K27ac积累并在基底细胞中变得更加突出，而H3K27me3在基底细胞中含量低，但在分化的上基底细胞类型中含量高。H4K20me3标记的组成型异染色质在妊娠后期分化的表皮细胞中也显着升高，表现出H4K16乙酰化的同时丧失。这些不同的染色质图谱在妊娠第15天时已在胚胎皮肤中建立，并在E18和产后皮肤中进一步扩增。我们的研究结果揭示了表皮祖细胞进入谱系并分化为分层表皮的不同细胞时发生的动态染色质状态，并为支持正常表皮发育和同源性的潜在表观遗传途径提供了见识。H4K20me3标记的组成型异染色质在妊娠后期分化的表皮细胞中也显着升高，表现出H4K16乙酰化的同时丧失。这些不同的染色质图谱在妊娠第15天时已在胚胎皮肤中建立，并在E18和产后皮肤中进一步扩增。我们的研究结果揭示了表皮祖细胞进入谱系并分化为分层表皮的不同细胞时发生的动态染色质状态，并为支持正常表皮发育和同源性的潜在表观遗传途径提供了见识。H4K20me3标记的组成型异染色质在妊娠后期分化的表皮细胞中也显着升高，表现出H4K16乙酰化的同时丧失。这些不同的染色质图谱在妊娠第15天时已在胚胎皮肤中建立，并在E18和产后皮肤中进一步扩增。我们的研究结果揭示了表皮祖细胞进入谱系并分化为分层表皮的不同细胞时发生的动态染色质状态，并为支持正常表皮发育和同源性的潜在表观遗传途径提供了见识。这些不同的染色质图谱在妊娠第15天时已在胚胎皮肤中建立，并在E18和产后皮肤中进一步扩增。我们的研究结果揭示了表皮祖细胞进入谱系并分化为分层表皮的不同细胞时发生的动态染色质状态，并为支持正常表皮发育和同源性的潜在表观遗传途径提供了见识。这些不同的染色质图谱在妊娠第15天时已在胚胎皮肤中建立，并在E18和产后皮肤中进一步扩增。我们的研究结果揭示了表皮祖细胞进入谱系并分化为分层表皮的不同细胞时发生的动态染色质状态，并为支持正常表皮发育和同源性的潜在表观遗传途径提供了见识。