Open AccessBinary transgenic mouse model for studying the trans control of globin gene switching: Evidence that GATA-1 is an in vivo repressor of human ɛ gene expression
Author(s) -
Qiliang Li,
Christopher H. Clegg,
Kenneth R. Peterson,
Sara E. Shaw,
Natacha Raich,
George Stamatoyannopoulos
Publication year - 1997
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.94.6.2444
Subject(s) - repressor , gene , biology , gene expression , genetically modified mouse , in vivo , transgene , regulation of gene expression , genetics , globin , microbiology and biotechnology
To test whether human GATA-1 (hGATA-1) is involved in the transcriptional control of globin gene switching, we produced transgenic mice overexpressing hGATA-1, crossed them with mice carrying a human β-globin locus yeast artificial chromosome (βYAC), and analyzed globin gene expression in their progeny. Mice carrying both the hGATA-1 and the βYAC transgenes had normal levels of γ- and β-globin mRNA and no distortion in the rate or in the timing of γ-to-β switch, indicating that hGATA-1 is not involved in the developmental control of γ- and β-globin genes. In contrast, mice carrying the hGATA-1 and the βYAC transgenes had 5- to 6-fold lower expression of the human ɛ globin gene compared with βYAC mice lacking the hGATA-1 transgene. These results provide directin vivo evidence that hGATA-1 is a specific repressor of human ɛ gene expression. Our findings also suggest that binary transgenic mouse systems based on overexpression of transcriptional factors can be used to investigate the trans control of human globin gene switching. Systems as the one we describe here should be useful in the study of any developmentally controlled human gene for which transgenic mice are available.