Tpr Deficiency Disrupts Erythroid Maturation With Impaired Chromatin Condensation in Zebrafish Embryogenesis

• Published in: Frontiers in cell and developmental biology 2021-10, Vol.9, p.709923-709923
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Cell and Developmental Biology; chromatin condensation; erythrocytes; erythroid maturation; Tpr; zebrafish
• ISSN: 2296-634X; 2296-634X
• DOI: 10.3389/fcell.2021.709923

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.