Deyrieux Adeline F, Wilson Van G
Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M Health Science Center, 8447 HWY 47, Bryan, TX, 77807-1359, USA.
Adv Exp Med Biol. 2017;963:197-214. doi: 10.1007/978-3-319-50044-7_12.
Tissue morphogenesis is a fascinating aspect of both developmental biology and regeneration of certain adult organs, and timely control of cellular differentiation is a key to these processes. During development, events interrupting cellular differentiation and leading to organ failure are embryonic lethal; likewise, perturbation of differentiation in regenerating tissues leads to dysfunction and disease. At the molecular level, cellular differentiation is orchestrated by a well-coordinated cascade of transcription factors (TFs) and chromatin remodeling complexes that drive gene expression. Altering the localization, stability, or activity of these regulatory elements can affect the sequential organization of the gene expression program and result in failed or abnormal tissue development. An accumulating body of evidence shows that the sumoylation system is a critical modulator of these regulatory cascades. For example, inhibition of the sumoylation system during embryogenesis causes lethality and/or severe abnormalities from invertebrates to mammals. Mechanistically, it is now known that many of the TFs and components of chromatin remodeling complexes that are critical for development and differentiation are targets for SUMO modification, though the specific functional consequences of the modifications remain uncharacterized in many cases. This chapter will address several of the models systems that have been examined for the role of sumoylation in differentiation and development. Understanding the profound regulatory role of SUMO in different tissues should lead not only to a better understanding of developmental biology, stem cell linage control, and the mechanisms of cellular differentiation, but may also lead to the identification of new targets for drug therapy and/or therapeutic manipulation of damaged organs and tissues.
组织形态发生是发育生物学和某些成体器官再生中一个引人入胜的方面，而细胞分化的适时控制是这些过程的关键。在发育过程中，中断细胞分化并导致器官衰竭的事件是胚胎致死性的；同样，再生组织中分化的扰动会导致功能障碍和疾病。在分子水平上，细胞分化是由一系列协调良好的转录因子（TFs）和染色质重塑复合物精心编排的，这些复合物驱动基因表达。改变这些调控元件的定位、稳定性或活性会影响基因表达程序的顺序组织，并导致组织发育失败或异常。越来越多的证据表明，SUMO化系统是这些调控级联反应的关键调节因子。例如，在胚胎发生过程中抑制SUMO化系统会导致从无脊椎动物到哺乳动物的致死性和/或严重异常。从机制上讲，现在已知许多对发育和分化至关重要的转录因子和染色质重塑复合物的成分是SUMO修饰的靶点，尽管在许多情况下这些修饰的具体功能后果仍未明确。本章将探讨几个已被研究的SUMO化在分化和发育中作用的模型系统。了解SUMO在不同组织中的深远调控作用不仅应该能更好地理解发育生物学、干细胞谱系控制和细胞分化机制，还可能导致识别药物治疗和/或受损器官和组织治疗操作的新靶点。
