I branching formation in erythroid differentiation is regulated by transcription factor C/EBPalpha.
The histo-blood group i and I antigens have been characterized as straight and branched repeats of N-acetyllactosamine, respectively, and the conversion of the straight-chain i to the branched-chain I structure on red cells is regulated to occur after birth. It has been demonstrated that the human I locus expresses 3 IGnT transcripts, IGnTA, IGnTB, and IGnTC, and that the last of these is responsible for the I branching formation on red cells. In the present investigation, the K-562 cell line was used as a model to show that the i-to-I transition in erythroid differentiation is determined by the transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha), which enhances transcription of the IGnTC gene, consequently leading to formation of the I antigen. Further investigation suggested that C/EBPalpha IGnTC-activation activity is modulated at a posttranslational level, and that the phosphorylation status of C/EBPalpha may have a crucial effect. Results from studies using adult and cord erythropoietic cells agreed with those derived using the K-562 cell model, with lentiviral expression of C/EBPalpha in CD34(+) hemopoietic cells demonstrating the determining role of C/EBPalpha in the induction of the IGnTC gene as well as in I antigen expression.
Twu
Yuh-Ching
YC
Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan.
Chen
Chie-Pein
CP
Hsieh
Chuang-Yi
CY
Tzeng
Cheng-Hwai
CH
Sun
Chien-Feng
CF
Wang
Shih-Hsin
SH
Chang
Mau-Sun
MS
Yu
Lung-Chih
LC
D000328:Adult; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000502:physiology*; D002454:Cell Differentiation; D004912:Erythrocytes / Q000166:cytology*; D005312:Fetal Blood; D015971:Gene Expression Regulation, Enzymologic; D006412:Hematopoietic Stem Cells; D006801:Humans; D007048:I Blood-Group System / Q000378:metabolism*; D020014:K562 Cells; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation
D022763:CCAAT-Enhancer-Binding Protein-alpha; D007048:I Blood-Group System; C106501:N-acetylglucosaminyltransferase IGnT; D017351:N-Acetylglucosaminyltransferases