An upstream, DNase I hypersensitive region of the hematopoietic-expressed transcription factor GATA-1 gene confers developmental specificity in transgenic mice

Michael A. Mcdevitt, Yuko Fujiwara, Ramesh A. Shivdasani, Stuart H. Orkin

Research output: Contribution to journalArticlepeer-review

Abstract

The transcription factor GATA-1, which is expressed in several hematopoietic lineages and multipotential progenitors, is required for the development of red blood cells and platelets. To identify control elements of the mouse GATA-1 gene, we analyzed DNase I hypersensitivity of the locus in erythroid chromatin and the expression of GATA-1/ Escherichia coli β-galactosidase (lacZ) transgenes in mice. Transgenes with 2.7 kb of promoter sequences are expressed infrequently and only within adult (definitive) erythroid cells. We show that inclusion of an upstream hypersensitive site (HS I) markedly enhances the frequency of expressing transgenic lines and activates expression in primitive erythroid cells. This pattern recapitulates the proper pattern of GATA-1 expression during development. By breeding a GATA-1/lacZ transgene into a GATA-1- background, we also have shown that the activation or maintenance of GATA-1 expression does not require the presence of GATA-1 itself, thereby excluding simple models of positive autoregulation. The transgene cassette reported here should be useful in directing expression of foreign sequences at the onset of hematopoiesis in the embryo and may assist in the identification of upstream regulators of the GATA-1 gene.

Original languageEnglish (US)
Pages (from-to)7976-7981
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number15
DOIs
StatePublished - Jul 22 1997

Keywords

  • Cis-elements
  • Erythropoiesis

ASJC Scopus subject areas

  • General

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