Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Dev Dyn. 2022 Sep;251(9):1490-1508. doi: 10.1002/dvdy.396. Epub 2021 Jul 17.
Animals develop skin regional specificities to best adapt to their environments. Birds are excellent models in which to study the epigenetic mechanisms that facilitate these adaptions. Patients suffering from SATB2 mutations exhibit multiple defects including ectodermal dysplasia-like changes. The preferential expression of SATB2, a chromatin regulator, in feather-forming compared to scale-forming regions, suggests it functions in regional specification of chicken skin appendages by acting on either differentiation or morphogenesis.
Retrovirus mediated SATB2 misexpression in developing feathers, beaks, and claws causes epidermal differentiation abnormalities (e.g. knobs, plaques) with few organ morphology alterations. Chicken β-keratins are encoded in 5 sub-clusters (Claw, Feather, Feather-like, Scale, and Keratinocyte) on Chromosome 25 and a large Feather keratin cluster on Chromosome 27. Type I and II α-keratin clusters are located on Chromosomes 27 and 33, respectively. Transcriptome analyses showed these keratins (1) are often tuned up or down collectively as a sub-cluster, and (2) these changes occur in a temporo-spatial specific manner.
These results suggest an organizing role of SATB2 in cluster-level gene co-regulation during skin regional specification.
动物形成皮肤区域特异性以适应环境。鸟类是研究促进这些适应性的表观遗传机制的理想模型。患有 SATB2 突变的患者表现出多种缺陷,包括外胚层发育不良样改变。SATB2 是一种染色质调节因子,在形成羽毛的区域与形成鳞片的区域相比优先表达,这表明它通过作用于分化或形态发生来参与鸡皮肤附属物的区域特化。
逆转录病毒介导的 SATB2 在发育中的羽毛、喙和爪中的异常表达导致表皮分化异常(如小结节、斑块),很少有器官形态改变。鸡 β-角蛋白编码在染色体 25 上的 5 个亚簇(爪、羽毛、羽毛样、鳞片和角蛋白细胞)和染色体 27 上的一个大羽毛角蛋白簇中。I 型和 II 型 α-角蛋白簇分别位于染色体 27 和 33 上。转录组分析表明,这些角蛋白(1)通常作为一个亚簇被集体上调或下调,(2)这些变化以时空特异性的方式发生。
这些结果表明 SATB2 在皮肤区域特化过程中对簇级基因共调控具有组织作用。