Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN, México City, Mexico.
J Cell Physiol. 2024 Feb;239(2):e31167. doi: 10.1002/jcp.31167. Epub 2023 Dec 21.
The understanding of the mechanisms that regulate gene expression to establish differentiation programs and determine cell lineages, is one of the major challenges in Developmental Biology. Besides the participation of tissue-specific transcription factors and epigenetic processes, the role of general transcription factors has been ignored. Only in recent years, there have been scarce studies that address this issue. Here, we review the studies on the biological activity of some TATA-box binding protein (TBP)-associated factors (TAFs) during the proliferation of stem/progenitor cells and their involvement in cell differentiation. Particularly, the accumulated evidence suggests that TAF4, TAF4b, TAF7L, TAF8, TAF9, and TAF10, among others, participate in nervous system development, adipogenesis, myogenesis, and epidermal differentiation; while TAF1, TAF7, TAF15 may be involved in the regulation of stem cell proliferative abilities and cell cycle progression. On the other hand, evidence suggests that TBP variants such as TBPL1 and TBPL2 might be regulating some developmental processes such as germ cell maturation and differentiation, myogenesis, or ventral specification during development. Our analysis shows that it is necessary to study in greater depth the biological function of these factors and its participation in the assembly of specific transcription complexes that contribute to the differential gene expression that gives rise to the great diversity of cell types existing in an organism. The understanding of TAFs' regulation might lead to the development of new therapies for patients which suffer from mutations, alterations, and dysregulation of these essential elements of the transcriptional machinery.
理解调节基因表达的机制,以建立分化程序并确定细胞谱系,是发育生物学的主要挑战之一。除了组织特异性转录因子和表观遗传过程的参与外,一般转录因子的作用一直被忽视。直到最近几年,才有一些研究探讨了这个问题。在这里,我们回顾了一些关于 TATA 框结合蛋白(TBP)相关因子(TAFs)在干细胞/祖细胞增殖过程中的生物学活性及其在细胞分化中的作用的研究。特别是,越来越多的证据表明,TAF4、TAF4b、TAF7L、TAF8、TAF9 和 TAF10 等因子参与了神经系统发育、脂肪生成、肌生成和表皮分化;而 TAF1、TAF7 和 TAF15 可能参与调节干细胞增殖能力和细胞周期进程。另一方面,有证据表明 TBP 变体,如 TBPL1 和 TBPL2,可能参与了一些发育过程的调控,如生殖细胞成熟和分化、肌生成或发育过程中的腹侧特化。我们的分析表明,有必要更深入地研究这些因子的生物学功能及其在组装特定转录复合物中的参与,这些复合物有助于产生生物体中存在的大量不同类型的细胞的差异基因表达。对 TAFs 调节的理解可能为患有这些转录机器基本元件突变、改变和失调的患者开发新的治疗方法提供指导。