title: I branching formation in erythroid differentiation is regulated by transcription factor C/EBPalpha.
abstract: 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.
authors.affiliation: Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan.
authors.forename: Yuh-Ching
authors.initials: YC
authors.lastname: Twu
authors.forename: Chie-Pein
authors.initials: CP
authors.lastname: Chen
authors.forename: Chuang-Yi
authors.initials: CY
authors.lastname: Hsieh
authors.forename: Cheng-Hwai
authors.initials: CH
authors.lastname: Tzeng
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Sun
authors.forename: Shih-Hsin
authors.initials: SH
authors.lastname: Wang
authors.forename: Mau-Sun
authors.initials: MS
authors.lastname: Chang
authors.forename: Lung-Chih
authors.initials: LC
authors.lastname: Yu
mesh_terms: 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
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D007048:I Blood-Group System; C106501:N-acetylglucosaminyltransferase IGnT; D017351:N-Acetylglucosaminyltransferases