Abstract：
Krüppel-like factor 1 (KLF1) plays a crucial role in erythropoiesis. In-depth studies conducted on mice and humans have highlighted its importance in erythroid lineage commitment, terminal erythropoiesis progression and the switching of globin genes from γ to β. The role of KLF1 in haemoglobin switching is exerted by the direct activation of β-globin gene and by the silencing of γ-globin through activation of BCL11A, an important γ-globin gene repressor. The link between KLF1 and γ-globin silencing identifies this transcription factor as a possible therapeutic target for β-hemoglobinopathies. Moreover, several mutations have been identified in the human genes that are responsible for various benign phenotypes and erythroid disorders. The study of the phenotype associated with each mutation has greatly contributed to the current understanding of the complex role of KLF1 in erythropoiesis. This review will focus on some of the principal functions of KLF1 on erythroid cell commitment and differentiation, spanning from primitive to definitive erythropoiesis. The fundamental role of KLF1 in haemoglobin switching will be also highlighted. Finally, an overview of the principal human mutations and relative phenotypes and disorders will be described.
摘要：
Krüppel样因子1（KLF1）在红细胞生成中起着至关重要的作用。对小鼠和人类进行的深入研究强调了其在类红细胞谱系承诺中的重要性，终末红细胞生成进展和珠蛋白基因从γ到β的转换。KLF1在血红蛋白转换中的作用是通过β-珠蛋白基因的直接激活和通过BCL11A的激活而沉默γ-珠蛋白，一种重要的γ-珠蛋白基因阻遏物。KLF1和γ-珠蛋白沉默之间的联系将该转录因子鉴定为β-血红蛋白病的可能治疗靶标。此外，已经在人类基因中发现了几种突变，这些突变是导致各种良性表型和红系疾病的原因。与每个突变相关的表型的研究极大地促进了目前对KLF1在红细胞生成中的复杂作用的理解。本文将重点介绍KLF1在红系细胞分化和分化中的一些主要功能。从原始红细胞生成到确定红细胞生成。还将强调KLF1在血红蛋白转换中的基本作用。最后,将描述主要的人类突变和相对表型和疾病的概述。
