Identification of human GATA-2 gene distal IS exon and its expression in hematopoietic stem cell fractions

Xiaoqing Pan, Naoko Minegishi, Hideo Harigae, Hironori Yamagiwa, Masayoshi Minegishi, Yasuyuki Akine, Masayuki Yamamoto

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Transcription factor GATA-2 is essential for the proper function of hematopoietic stem cells and progenitors. Two first exons/promoters have been found in the mouse GATA-2 gene, and a distal IS promoter shows activity specific to hematopoietic progenitors and neural tissues. To ascertain whether the two-promoter system is also utilized in the human GATA-2 gene, we isolated and analyzed a P1 phage clone containing this gene. The nucleotide sequence of the human GATA-2 gene 5' flanking region was determined over 10 kbp, and a human IS exon was identified in the locus through sequence comparison analysis with that of the mouse GATA-2 IS exon. RNA blotting and reverse-transcribed PCR analyses identified a transcript that starts from the IS exon in human leukemia-derived cell lines. The IS-originated transcript was also identified in CD34-positive bone marrow and cord blood mononuclear cells, which are recognized as clinically important hematopoietic stem cell- enriched fractions. Phylogenic comparison of the human and mouse GATA-2 gene sequences revealed several regions in the locus that exhibit high sequence similarity. These results demonstrate that the GATA-2 gene regulatory machinery is conserved among vertebrates. The fact that the human IS promoter is active in the hematopoietic stem cell/progenitor fraction may be an important clue for the design of a vector system that can specifically express various genes in hematopoietic stem cells and progenitors.

Original languageEnglish
Pages (from-to)105-112
Number of pages8
JournalJournal of biochemistry
Volume127
Issue number1
DOIs
Publication statusPublished - 2000 Jan 1

Keywords

  • GATA-2
  • Hematopoietic stem cell
  • Nucleotide sequence
  • Promoter
  • Transcriptional regulation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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