J. Biochem, 2000, Vol. 127, No. 1 105-112
© 2000 Japanese Biochemical Society
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Identification of Human GATA-2 Gene Distal IS Exon and Its Expression in Hematopoietic Stem Cell Fractions1
*Institutes of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance (TARA) Tsukuba 305-8577
Institute of Clinical Medicine, University of Tsukuba Tsukuba 305-8577
Department of Clinical Chemistry, School of Medicine, Sendai 980-7700
Institute of Aging, Cancer and Developmental Biology, Tohoku University Sendai 980-7700
2 To whom correspondence should be addressed. Phone: +81-298-53-6158, Fax: +81-298-53-7318, E-mail:masi{at}tara.tsukuba.ac.jp
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-pos-itive 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.
1 This work was supported in part by a research grant from the Ichiro Kanehara Foundation; a grant from Rotary Yoneyama Memorial Foundation; Grants-in-Aid from the Ministry of Education, Science, Sports and Culture; CREST and the Japanese Society for Promotion of Sciences (JSPS Research for the Future Project).
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