Transcriptional regulation of cell type-specific expression of the TATA- less A subunit gene for human coagulation factor XIII

Masafumi Kida, Masayoshi Souri, Masayuki Yamamoto, Hidehiko Saito, Akitada Ichinose

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)6138-6147
Number of pages10
JournalJournal of Biological Chemistry
Volume274
Issue number10
DOIs
Publication statusPublished - 1999 Mar 5
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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