Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Joint Graduate Program of Peking-Tsinghua-NIBS, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Acta Biochim Biophys Sin (Shanghai). 2018 Jan 1;50(1):60-67. doi: 10.1093/abbs/gmx122.
The transforming growth factor beta (TGF-β) family of ligands plays major roles in embryonic development, tissue homeostasis, adult immunity, and wound repair. Dysregulation of TGF-β signaling pathway leads to severe diseases. Its key components have been revealed over the past two decades. This family of cytokines acts by activating receptor activated SMAD (R-SMAD) transcription factors, which in turn modulate the expression of specific sets of target genes. Cells of a multicellular organism have the same genetic information, yet they show structural and functional differences owing to differential expression of their genes. Studies have demonstrated that epigenetic regulation, an integral part of the TGF-β signaling, enables cells to sense and respond to TGF-β signaling in a cell context-dependent manner. R-SMAD, as the central transcription factor of TGF-β signaling, can recruit various epigenetic regulators to shape the transcriptome. In this review, we focus on epigenetic regulatory mechanisms in the TGF-β signaling during mammalian development and diseases and discuss the central role of the interaction between R-SMAD and various epigenetic regulators in this epigenetic regulation. The crosstalk between TGF-β signaling and the epigenome could serve as a versatile fine-tuning mechanism for transcriptional regulation during embryonic development and progression of diseases, particularly cancer.
转化生长因子 β（TGF-β）配体家族在胚胎发育、组织稳态、成人免疫和伤口修复中发挥重要作用。TGF-β 信号通路的失调会导致严重的疾病。在过去的二十年中，其关键成分已经被揭示。该细胞因子家族通过激活受体激活的 SMAD（R-SMAD）转录因子发挥作用，而这些转录因子反过来又调节特定靶基因的表达。多细胞生物的细胞具有相同的遗传信息，但由于基因的差异表达，它们表现出结构和功能上的差异。研究表明，表观遗传调控是 TGF-β 信号的一个组成部分，它使细胞能够以细胞上下文依赖的方式感知和响应 TGF-β 信号。R-SMAD 作为 TGF-β 信号的核心转录因子，可以招募各种表观遗传调节剂来塑造转录组。在这篇综述中，我们重点讨论了哺乳动物发育和疾病过程中 TGF-β 信号中的表观遗传调控机制，并讨论了 R-SMAD 与各种表观遗传调节剂之间的相互作用在这种表观遗传调控中的核心作用。TGF-β 信号与表观基因组之间的串扰可以作为胚胎发育和疾病进展过程中（尤其是癌症）转录调控的一种多功能微调机制。
