Advanced Medical Initiatives, Division of Hematopoietic Stem Cells, Department of Advanced Medical Initiatives, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
Cell Biol Int. 2012 Feb;36(2):195-202. doi: 10.1042/CBI20110169.
Hmgn2 (high mobility group nucleosomal 2), a ubiquitous nucleosome-binding protein that unfolds chromatin fibres and enhances DNA replication, reportedly regulates differentiation of epithelial and mesenchymal cells. To investigate how Hmgn2 regulates HC (haemopoietic cell) differentiation, we quantified Hmgn2 expression in HCs of mouse FL (fetal liver) during erythroid differentiation. Hmgn2 expression levels were >10-fold higher in immature erythroid progenitors than in mature erythroid cells, suggesting that Hmgn2 antagonizes erythroid differentiation. To address this issue, Hmgn2 were transfected into both Friend erythroleukaemia cells and FL HCs. There was a 3.3-fold decrease in relatively mature c-Kit(+)/CD71(+) erythroid cells, a 2.9-fold increase in immature c-Kit(+)/CD71(-) erythroid cells in transfected Friend cells, a 1.1-fold decrease in relatively mature CD71(+)/Ter119(+) erythroid cells, and a 1.7-fold increase in relatively immature c-Kit(+)/CD71(+) erythroid cells in FL HCs accompanied by down-regulation of genes encoding the erythroid transcription factors, Gata1 and Klf1. Two days after Hmgn2 transfection of Friend erythroleukaemia cells, the number of S-phase cells increased, whereas the number of cells in G(1) decreased, while that of mitotic cells remained unchanged. We conclude that ectopic expression of Hmgn2 antagonizes mouse erythroid differentiation in vitro, which may be due to enhancement of DNA replication and/or blocking entry of mitosis at S-phase.
Hmgn2（高迁移率族核小体 2）是一种普遍存在的核小体结合蛋白，可展开染色质纤维并增强 DNA 复制，据报道可调节上皮和间充质细胞的分化。为了研究 Hmgn2 如何调节 HC（造血细胞）分化，我们在小鼠 FL（胎肝）中红细胞分化期间量化了 Hmgn2 在 HC 中的表达。未成熟的红细胞祖细胞中的 Hmgn2 表达水平比成熟的红细胞细胞高 10 倍以上，这表明 Hmgn2 拮抗红细胞分化。为了解决这个问题，我们将 Hmgn2 转染到 Friend 红白血病细胞和 FL HC 中。转染的 Friend 细胞中相对成熟的 c-Kit（+）/CD71（+）红细胞细胞减少了 3.3 倍，未成熟的 c-Kit（+）/CD71（-）红细胞细胞增加了 2.9 倍，相对成熟的 CD71（+）/Ter119（+）红细胞细胞减少了 1.1 倍，相对不成熟的 c-Kit（+）/CD71（+）红细胞细胞增加了 1.7 倍，同时编码红细胞转录因子 Gata1 和 Klf1 的基因下调。在 Friend 红白血病细胞中转染 Hmgn2 两天后，S 期细胞的数量增加，而 G1 期细胞的数量减少，而有丝分裂细胞的数量保持不变。我们得出结论，Hmgn2 的异位表达在体外拮抗小鼠红细胞分化，这可能是由于增强了 DNA 复制和/或阻止了 S 期有丝分裂的进入。
