title: Ectopic expression of Hmgn2 antagonizes mouse erythroid differentiation in vitro.
abstract: 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.
authors: Advanced Medical Initiatives, Division of Hematopoietic Stem Cells, Department of Advanced Medical Initiatives, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Kasem
authors: K
authors: Kulkeaw
authors: Tomoko
authors: T
authors: Inoue
authors: Chiyo
authors: C
authors: Mizuochi
authors: Yuka
authors: Y
authors: Horio
authors: Yasushi
authors: Y
authors: Ishihama
authors: Daisuke
authors: D
authors: Sugiyama
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001789:Blood Group Antigens / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D041905:Erythroid Cells / Q000166:cytology*; D050982:GATA1 Transcription Factor / Q000378:metabolism; D020869:Gene Expression Profiling; D024242:HMGN2 Protein / Q000235:genetics / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism; D016196:S Phase
chemical_list: D015703:Antigens, CD; D001789:Blood Group Antigens; C068126:CD71 antigen; D050982:GATA1 Transcription Factor; D024242:HMGN2 Protein; D051741:Kruppel-Like Transcription Factors; D011990:Receptors, Transferrin; C489122:TER-119 antigen, mouse; C080774:erythroid Kruppel-like factor; D019009:Proto-Oncogene Proteins c-kit