Transcription of human ABO histo-blood group genes is dependent upon binding of transcription factor CBF/NF-Y to minisatellite sequence.
We have studied the transcriptional regulatory mechanism of the human histo-blood group ABO genes, and identified DNA cis-elements and trans-activating protein that control the expression of these genes which are important in blood transfusion and organ transplantation. We introduced the 5'-upstream sequence of ABO genes into the promoterless reporter vector and characterized the promoter activity of deletion constructs using transient transfection assays with gastric cancer cell line KATO III cells. The sequence just upstream of the transcription start site (cap site), and an enhancer element, which is located further upstream (between -3899 and -3618 base pairs (bp) from the transcription initiation site) and contains 4 tandem copies of a 43-bp repeat unit, were shown in gastric cancer cells to be responsible for the transcriptional activity of the ABO genes. DNA binding studies have demonstrated that a transcription factor, CBF/NF-Y, bound to the 43-bp repeat unit in the minisatellite. Functional importance of these CBF/NF-Y-binding sites in enhancer activity was confirmed by transfection experiments using reporter plasmids with mutated binding sites. Thus, transcriptional regulation of the human ABO genes is dependent upon binding of CBF/NF-Y to the minisatellite.
Kominato
Y
Y
Toyama Medical and Pharmaceutical University, Faculty of Medicine, Department of Legal Medicine, Toyama, 930-01 Japan. ykomilm@ms.toyama-mpu.ac.jp
Tsuchiya
T
T
Hata
N
N
Takizawa
H
H
Yamamoto
F
F
D000017:ABO Blood-Group System / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D018598:Minisatellite Repeats; D008969:Molecular Sequence Data; D011485:Protein Binding; D012091:Repetitive Sequences, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D000017:ABO Blood-Group System; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors