A GATA box in the GATA-1 gene hematopoietic enhancer is a critical element in the network of GATA factors and sites that regulate this gene

Shigeko Nishimura, Satoru Takahashi, Takashi Kuroha, Naruyoshi Suwabe, Toshiro Nagasawa, Cecelia Trainor, Masayuki Yamamoto

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

A region located at kbp -3.9 to -2.6 5' to the first hematopoietic exon of the GATA-1 gene is necessary to recapitulate gene expression in both the primitive and definitive erythroid lineages. In transfection analyses, this region activated reporter gene expression from an artificial promoter in a position- and orientation-independent manner, indicating that the region functions as the GATA-1 gene hematopoietic enhancer (G1HE). However, when analyzed in transgenic embryos in vivo, G1HE activity was orientation dependent and also required the presence of the endogenous GATA-1 gene hematopoietic promoter. To define the boundaries of G1HE, a series of deletion constructs were prepared and tested in transfection and transgenic mice analyses. We show that G1HE contains a 149-bp core region which is critical for GATA-1 gene expression in both primitive and definitive erythroid cells but that expression in megakaryocytes requires the core plus additional sequences from G1HE. This core region contains one GATA, one GAT, and two E boxes. Mutational analyses revealed that only the GATA box is critical for gene-regulatory activity. Importantly, G1HE was active in SCL(- /-) embryos. These results thus demonstrate the presence of a critical network of GATA factors and GATA binding sites that controls the expression of this gene.

Original languageEnglish
Pages (from-to)713-723
Number of pages11
JournalMolecular and cellular biology
Volume20
Issue number2
DOIs
Publication statusPublished - 2000 Jan 1
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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