Laboratory of Immunology, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan.
Adv Exp Med Biol. 2024;1459:97-113. doi: 10.1007/978-3-031-62731-6_5.
Helix-loop-helix (HLH) transcription factors (TFs) play a key role in various cellular differentiation and function through the regulation of enhancer activity. E2A, a member of the mammalian E-protein family (class I HLH protein), is well known to play an important role in hematopoiesis, especially in adaptive lymphocyte development. E2A instructs B- and T-cell lineage development through the regulation of enhancer activity for B- or T-cell signature gene expression, including Rag1 and Rag2 (Rag1/2) genes. In this chapter, we mainly focus on the function of E2A in B-cell development and on the roles of E2A in establishing the enhancer landscape through the recruitment of EP300/KAT3B, chromatin remodeling complex, mediator, cohesion, and TET proteins. Finally, we demonstrate how E2A orchestrates the assembly of the Rag1/2 gene super-enhancer (SE) formation by changing the chromatin conformation across the Rag gene locus.
螺旋-环-螺旋 (HLH) 转录因子 (TF) 通过调节增强子活性在各种细胞分化和功能中发挥关键作用。E2A 是哺乳动物 E 蛋白家族 (I 类 HLH 蛋白) 的成员，众所周知，它在造血中发挥着重要作用，特别是在适应性淋巴细胞发育中。E2A 通过调节 B 细胞或 T 细胞特征基因表达的增强子活性来指导 B 细胞和 T 细胞谱系的发育，包括 Rag1 和 Rag2 (Rag1/2) 基因。在本章中，我们主要关注 E2A 在 B 细胞发育中的功能，以及 E2A 通过招募 EP300/KAT3B、染色质重塑复合物、中介体、黏合蛋白和 TET 蛋白来建立增强子景观的作用。最后，我们展示了 E2A 如何通过改变 Rag 基因座上的染色质构象来协调 Rag1/2 基因超增强子 (SE) 的形成。
