Wu Shuang, Chen Kai, Xu Tao, Ma Ke, Gao Lei, Fu Cong, Zhang Wenjuan, Jing Changbin, Ren Chunguang, Deng Min, Chen Yi, Zhou Yi, Pan Weijun, Jia Xiaoe
Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.
Central Laboratory, Qingdao Agricultural University, Qingdao, China.
Front Cell Dev Biol. 2021 Oct 13;9:709923. doi: 10.3389/fcell.2021.709923. eCollection 2021.
Vertebrate erythropoiesis involves nuclear and chromatin condensation at the early stages of terminal differentiation, which is a unique process to distinguish mature erythrocytes from erythroblasts. However, the underlying mechanisms of chromatin condensation during erythrocyte maturation remain elusive. Here, we reported a novel zebrafish mutant with erythroid maturation deficiency. Positional cloning showed that a single base mutation in gene, which encodes nucleoporin translocated promoter region (Tpr), is responsible for the disrupted erythroid maturation and upregulation of erythroid genes, including and . Further investigation revealed that deficient erythropoiesis in mutant was independent on HIF signaling pathway. The proportion of euchromatin was significantly increased, whereas the percentage of heterochromatin was markedly decreased in mutant. In addition, knockdown in human K562 cells also disrupted erythroid differentiation and dramatically elevated the expression of globin genes, which suggests that the functions of TPR in erythropoiesis are highly conserved in vertebrates. Taken together, this study revealed that Tpr played vital roles in chromatin condensation and gene regulation during erythroid maturation in vertebrates.
脊椎动物的红细胞生成在终末分化的早期阶段涉及细胞核和染色质浓缩，这是将成熟红细胞与成红细胞区分开来的独特过程。然而，红细胞成熟过程中染色质浓缩的潜在机制仍然不清楚。在这里，我们报道了一种具有红细胞成熟缺陷的新型斑马鱼突变体。定位克隆表明，编码核孔蛋白易位启动子区域（Tpr）的基因中的单个碱基突变，是导致红细胞成熟受阻和包括……等红细胞基因上调的原因。进一步研究表明，……突变体中红细胞生成不足与低氧诱导因子（HIF）信号通路无关。在……突变体中，常染色质的比例显著增加，而异染色质的百分比则明显降低。此外，在人K562细胞中敲低……也会破坏红细胞分化，并显著提高珠蛋白基因的表达，这表明TPR在红细胞生成中的功能在脊椎动物中高度保守。综上所述，这项研究揭示了Tpr在脊椎动物红细胞成熟过程中的染色质浓缩和基因调控中起着至关重要的作用。
