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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4526-4534.
Prepublished online as a Blood First Edition Paper on September 13, 2007; DOI 10.1182/blood-2007-01-067801.
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TRANSFUSION MEDICINE
I branching formation in erythroid differentiation is regulated by transcription factor C/EBP
Yuh-Ching Twu1,
Chie-Pein Chen2,3,
Chuang-Yi Hsieh1,
Cheng-Hwai Tzeng4,5,
Chien-Feng Sun6,7,
Shih-Hsin Wang8,
Mau-Sun Chang3, and
Lung-Chih Yu1,8
1 Institute of Biochemical Sciences, National Taiwan University, Taipei;
2 Division of High Risk Pregnancy, Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei;
3 Department of Medical Research, Mackay Memorial Hospital, Taipei;
4 Section of Transfusion Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei;
5 College of Medicine, National Yang-Ming University, Taipei;
6 Department of Clinical Pathology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan;
7 Department of Pathology, School of Medicine, Chang Gung University, Taoyuan; and
8 Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
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  (C/EBP), which enhances transcription of the IGnTC gene, consequently leading to formation of the I antigen. Further investigation suggested that C/EBP IGnTC-activation activity is modulated at a posttranslational level, and that the phosphorylation status of C/EBP 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/EBP in CD34+ hemopoietic cells demonstrating the determining role of C/EBP in the induction of the IGnTC gene as well as in I antigen expression.
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