Ectopic expression of Hmgn2 antagonizes mouse ervthroid differentiation in vitrn
Ectopic expression of Hmgn2 antagonizes mouse ervthroid differentiation in vitrn
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Hmgn2的异位表达拮抗小鼠玻璃体内红细胞分化
DOI：
10.1042/cbi20110169
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发表时间：
2012
期刊：
影响因子：
3.9
通讯作者：
et al
中科院分区：
文献类型：
--
作者：
Kulkeaw;K.;Inoue;T.;et al
Hmgn 2（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，据报道可调节上皮细胞和间充质细胞的分化。为了研究Hmgn 2如何调节HC（造血细胞）分化，我们定量了红系分化过程中小鼠FL（胎肝）HC中Hmgn 2的表达。Hmgn 2在未成熟红系祖细胞中的表达水平比成熟红系细胞高10倍以上，表明Hmgn 2拮抗红系分化。为了解决这个问题，将Hmgn 2转染到Friend红白血病细胞和FL HC中。在转染的Friend细胞中，相对成熟的c-Kit +/CD 71+红系细胞减少3.3倍，未成熟的c-Kit +/CD 71 −红系细胞增加2.9倍，相对成熟的CD 71 +/Ter 119+红系细胞减少1.1倍，相对不成熟的c-Kit+/CD 71+增加了1.7倍FL HC中的红系细胞伴随着编码红系转录因子Gata 1和Klf 1的基因的下调。Friend红白血病细胞转染Hmgn 2后2天，S期细胞数量增加，而G1期细胞数量减少，而有丝分裂期细胞数量保持不变。我们的结论是Hmgn 2的异位表达拮抗小鼠红系细胞体外分化，这可能是由于DNA复制的增强和/或阻断S期有丝分裂的进入。
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 quantifiedHmgn2expression in HCs of mouse FL (fetal liver) during erythroid differentiation.Hmgn2expression levels were >10‐fold higher in immature erythroid progenitors than in mature erythroid cells, suggesting that Hmgn2 antagonizes erythroid differentiation. To address this issue,Hmgn2were 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 afterHmgn2transfection of Friend erythroleukaemia cells, the number of S‐phase cells increased, whereas the number of cells in G1decreased, while that of mitotic cells remained unchanged. We conclude that ectopic expression of Hmgn2 antagonizes mouse erythroid differentiationin vitro, which may be due to enhancement of DNA replication and/or blocking entry of mitosis at S‐phase.