Regulation of I Branching Formation in Erythroid Differentiation
Date Issued
2008
Date
2008
Author(s)
Twu, Yuh-Ching
Abstract
The human histo-blood group I and i antigens are characterized as branched andtraight chains of N-acetyllactosamine (Galβ1-4GlcNAc, LacNAc) repeat, respectively.etal and neonatal erythrocytes predominantly express i antigen, with only a smallmount of I. It has been recognized that the presence of the straight-chain i antigen onetal erythrocytes surface is one of the important mechanisms to prevent the hemolyticisease due to ABO incompatibility pregnancy. After birth, the i antigen of erythrocytes gradually converted to the branched I antigen; however, the regulatory mechanism forhe I branching formation awaits elucidation. Conversion of the straight-chain i to theranched I antigen is catalyzed by the enzyme encoded by the I locus, I-branching-1,6-N-acetylglucosaminyltransferase (IGnT). The human I locus expresses three IGnTranscripts, IGnTA, IGnTB, and IGnTC, which have different exon 1, but identical exon and exon 3 regions. In our previous study, we have demonstrated that IGnTC is thentrinsic gene responsible for the I antigen expression on erythrocytes.n this thesis, the erythroleukemia cell line K-562 was used as a model to study theegulatory mechanism of I antigen expression during erythroid differentiation. Ouresults demonstrated that the transcription factor CCAAT/enhancer binding protein αC/EBPα) stimulated the expression of IGnTC gene in sodium butyrate-inducedrythroid differentiation of K-562 cells, and consequently enhanced the I antigenxpression on the cell surfaces. The results obtained from chromatinmmunoprecipitation (ChIP) and immunoprecipitation (IP) analysis, suggested that thehosphorylation status of C/EBPα may affect its binding affinity onto the 5’ regulatoryegion of IGnTC gene and thus regulates the expression of IGnTC gene. Human adultnd cord CD34+ hemopoietic stem cells were employed to further investigate the role of/EBPα in the I antigen expression during erythroid differentiation, and lentiviralxpression system was used to introduce C/EBPα into adult and cord CD34+ cells. Theesults demonstrated that the transcription factor C/EBPα played the determining role inhe regulation of the I antigen expression during erythropoiesis. Furthermore, the resultsuggested that the function of C/EBPα in the IGnTC gene expression and theubsequent I antigen formation may be determined by the post-translationalodification status of C/EBPα. The post-translational modification and the mechanismeading to this modification on C/EBPα during erythroid differentiation await furthernvestigation, and it is of significance to further reveal the possible difference of thisechanism between adult and fetal erythropoiesis processes. Only after the elucidationhese mechanisms of the post-translational modification on C/EBPα the mechanismseading to the predominant expression of straight-chain i antigen on fetal erythrocytesnd the i-to-I conversion after birth could be answered in more detail.
Subjects
I antigen
erythroid differentiation
File(s)![Thumbnail Image]()
Loading...
Name
ntu-97-D92B46003-1.pdf
Size
23.32 KB
Format
Adobe PDF
Checksum
(MD5):9ff09973e96086b7e3670d22bea28d0a