Open AccessAnalysis of the human alpha-globin gene cluster in transgenic mice.
Author(s) -
Jacqueline A. Sharpe,
Dominic J. Wells,
Emma Whitelaw,
Paresh Vyas,
Douglas R. Higgs,
W. G. Wood
Publication year - 1993
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.90.23.11262
Subject(s) - gene , biology , locus control region , regulatory sequence , microbiology and biotechnology , locus (genetics) , globin , transgene , gene cluster , gene expression , regulation of gene expression , alpha globulin , genetically modified mouse , hypersensitive site , alpha (finance) , genetics , promoter , medicine , construct validity , nursing , patient satisfaction
A 350-bp segment of DNA associated with an erythroid-specific DNase I-hypersensitive site (HS-40), upstream of the alpha-globin gene cluster, has been identified as the major tissue-specific regulator of the alpha-globin genes. However, this element does not direct copy number-dependent or developmentally stable expression of the human genes in transgenic mice. To determine whether additional upstream hypersensitive sites could provide more complete regulation of alpha gene expression we have studied 17 lines of transgenic mice bearing various DNA fragments containing HSs -33, -10, -8, and -4, in addition to HS -40. Position-independent, high-level expression of the human zeta- and alpha-globin genes was consistently observed in embryonic erythroid cells. However, the additional HSs did not confer copy-number dependence, alter the level of expression, or prevent the variable down-regulation of expression in adults. These results suggest that the region upstream of the human alpha-globin genes is not equivalent to that upstream of the beta locus and that although the two clusters are coordinately expressed, there may be differences in their regulation.