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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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Submitted January 12, 2007
Accepted August 23, 2007
I branching formation in erythroid differentiation is regulated by transcription factor C/EBP
Yuh-Ching Twu, Chie-Pein Chen, Chuang-Yi Hsieh, Cheng-Hwai Tzeng, Chien-Feng Sun, Shih-Hsin Wang, Mau-Sun Chang, and Lung-Chih Yu*
Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan
Division of High Risk Pregnancy, Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan
Section of Transfusion Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
Department of Clinical Pathology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
* Corresponding author; email: yulc{at}ntu.edu.tw.
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 post-translational level, and that the phosphorylation status of C/EBP may have a crucial effect. Results from studies employing the 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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