Department of Eukaryotic Genetics, Institute of Biomedical Genetics, University of Stuttgart, Stuttgart, Germany.
Adv Exp Med Biol. 2024;1459:243-258. doi: 10.1007/978-3-031-62731-6_11.
Lineage-specific transcription factors (TFs) regulate differentiation of hematopoietic stem cells (HSCs). They are decisive for the establishment and maintenance of lineage-specific gene expression programs during hematopoiesis. For this they create a regulatory network between TFs, epigenetic cofactors, and microRNAs. They activate cell-type specific genes and repress competing gene expression programs. Disturbance of this process leads to impaired lineage fidelity and diseases of the blood system. The TF T-cell acute leukemia 1 (TAL1) is central for erythroid differentiation and contributes to the formation of distinct gene regulatory complexes in progenitor cells and erythroid cells. A TAL1/E47 heterodimer binds to DNA with the TFs GATA-binding factor 1 and 2 (GATA1/2), the cofactors LIM domain only 1 and 2 (LMO1/2), and LIM domain-binding protein 1 (LDB1) to form a core TAL1 complex. Furthermore, cell-type-dependent interactions of TAL1 with other TFs such as with runt-related transcription factor 1 (RUNX1) and Kruppel-like factor 1 (KLF1) are established. Moreover, TAL1 activity is regulated by the formation of TAL1 isoforms, posttranslational modifications (PTMs), and microRNAs. Here, we describe the function of TAL1 in normal hematopoiesis with a focus on erythropoiesis.
谱系特异性转录因子（TFs）调节造血干细胞（HSCs）的分化。它们对于造血过程中谱系特异性基因表达程序的建立和维持至关重要。为此，它们在 TF、表观遗传共因子和 microRNAs 之间创建了一个调节网络。它们激活细胞类型特异性基因并抑制竞争基因表达程序。这个过程的干扰会导致谱系保真度受损和血液系统疾病。TF T 细胞急性白血病 1（TAL1）是红细胞分化的核心，有助于在祖细胞和红细胞中形成不同的基因调控复合物。TAL1/E47 异二聚体与 TF GATA 结合因子 1 和 2（GATA1/2）、共因子 LIM 结构域仅 1 和 2（LMO1/2）以及 LIM 结构域结合蛋白 1（LDB1）结合，形成核心 TAL1 复合物。此外，TAL1 与其他 TF（如 runt 相关转录因子 1（RUNX1）和 Kruppel 样因子 1（KLF1））的细胞类型依赖性相互作用也被建立。此外，TAL1 的活性受 TAL1 异构体的形成、翻译后修饰（PTMs）和 microRNAs 的调节。本文将重点介绍 TAL1 在正常造血中的功能，特别是在红细胞生成中的作用。
