Laboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Biodata Mining and Discovery Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
J Invest Dermatol. 2023 Jul;143(7):1220-1232.e9. doi: 10.1016/j.jid.2022.12.020. Epub 2023 Jan 26.
Chromatin landscape and regulatory networks are determinants in lineage specification and differentiation. To define the temporospatial differentiation axis in murine epidermal cells in vivo, we generated datasets profiling expression dynamics (RNA sequencing), chromatin accessibility (assay for transposase-accessible chromatin using sequencing), architecture (Hi-C), and histone modifications (chromatin immunoprecipitation followed by sequencing) in the epidermis. We show that many differentially regulated genes are suppressed during the differentiation process, with superenhancers controlling differentiation-specific epigenomic changes. Our data shows the relevance of the Dlx/Klf/Grhl combinatorial regulatory network in maintaining correct temporospatial gene expression during epidermal differentiation. We determined differential open compartments, topologically associating domain score, and looping in the basal cell and suprabasal cell epidermal fractions, with the evolutionarily conserved epidermal differentiation complex region showing distinct suprabasal cell-specific topologically associating domain and loop formation that coincided with superenhancer sites. Overall, our study provides a global genome-wide resource of chromatin dynamics that define unrecognized regulatory networks and the epigenetic control of Dlx3-bound superenhancer elements during epidermal differentiation.
染色质景观和调控网络是谱系特化和分化的决定因素。为了在体内定义小鼠表皮细胞的时空分化轴，我们生成了一系列数据集，用于分析基因表达动态（RNA 测序）、染色质可及性（使用测序的转座酶可及染色质测定法）、结构（Hi-C）和组蛋白修饰（染色质免疫沉淀测序）在表皮中的情况。我们表明，许多差异调节的基因在分化过程中被抑制，超级增强子控制分化特异性的表观遗传变化。我们的数据表明，Dlx/Klf/Grhl 组合调控网络在维持表皮分化过程中正确的时空基因表达方面具有重要意义。我们确定了在基底细胞和超基底细胞表皮部分中的差异开放隔间、拓扑关联域评分和环化，进化上保守的表皮分化复合物区域显示出独特的超基底细胞特异性拓扑关联域和环化形成，与超级增强子位点一致。总的来说，我们的研究提供了一个全面的染色质动态基因组资源，定义了未被识别的调控网络和表皮分化过程中 Dlx3 结合的超级增强子元件的表观遗传控制。
