Transcriptional regulation of cell type-specific expression of the TATA-less A subunit gene for human coagulation factor XIII.
To study the mechanism of gene regulation for coagulation factor XIII A subunit (FXIIIA), we characterized its 5'-flanking region using a monocytoid (U937), a megakaryocytoid (MEG-01), and other cells. Our results confirmed that U937 and MEG-01 contained FXIIIA mRNA. A tentative transcription start site was determined to be 76 bases upstream from the first exon/intron boundary. Reporter gene assays revealed that a 5'-fragment (-2331 to +75) was sufficient to support basal expression in U937 and MEG-01 but not in the other cells. Deletion analysis confined a minimal promoter sequence from -114 to +75. DNase footprinting, electrophoretic mobility shift, and reporter gene assays demonstrated that promoter elements for a myeloid-enriched transcription factor (MZF-1-like protein) and two ubiquitous transcription factors (NF-1 and SP-1) in this region were important for the basal FXIII expression. It was also revealed that an upstream region (-806 to -290) had enhancer activity in MEG-01 but silencer activity in U937. DNA sequences for binding of myeloid-enriched factors (GATA-1 and Ets-1) were recognized in this region, and the GATA-1 element was found to be responsible for the enhancer activity. These transcription factors play a major role in the cell type-specific expression of FXIIIA, which differs from other transglutaminases.
Department of Molecular Pathological Biochemistry and Biology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.
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M
Kida
M
M
Souri
M
M
Yamamoto
H
H
Saito
A
A
Ichinose
D001483:Base Sequence; D005176:Factor XIII / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009841:Oligonucleotides; D009928:Organ Specificity; D016385:TATA Box / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D020298:U937 Cells
D009841:Oligonucleotides; D005176:Factor XIII