The T cell-specific DNA-binding protein TCF-1 is a central regulator of T cell development and function along multiple stages and lineages. Because it interacts with β-catenin, TCF-1 has been classically viewed as a downstream effector of canonical Wnt signaling, although there is strong evidence for β-catenin-independent TCF-1 functions. TCF-1 co-binds accessible regulatory regions containing or lacking its conserved motif and cooperates with other nuclear factors to establish context-dependent epigenetic and transcription programs that are essential for T cell development and for regulating immune responses to infection, autoimmunity and cancer. Although it has mostly been associated with positive regulation of chromatin accessibility and gene expression, TCF-1 has the potential to reduce chromatin accessibility and thereby suppress gene expression. In addition, the binding of TCF-1 bends the DNA and affects the chromatin conformation genome wide. This Review discusses the current understanding of the multiple roles of TCF-1 in T cell development and function and their mechanistic underpinnings.

T 细胞特异性 DNA 结合蛋白 TCF-1 是 T 细胞在多个阶段和谱系中发育和发挥功能的中央调节因子。因为它与 β-连环蛋白相互作用，TCF-1 一直被经典地视为典型 Wnt 信号传导的下游效应子，尽管有强有力的证据表明 β-连环蛋白独立的 TCF-1 功能。TCF-1 共同结合含有或缺乏其保守基序的可及调节区域，并与其他核因子合作建立上下文相关的表观遗传和转录程序，这些程序对于 T 细胞发育和调节对感染、自身免疫和癌症的免疫反应至关重要。尽管它主要与染色质可及性和基因表达的正调控有关，TCF-1 有可能降低染色质的可及性，从而抑制基因表达。此外，TCF-1 的结合会弯曲 DNA 并影响整个基因组的染色质构象。本综述讨论了目前对 TCF-1 在 T 细胞发育和功能中的多重作用及其机制基础的理解。