A minimal ankyrin promoter linked to a human γ-globin gene demonstrates erythroid specific copy number dependent expression with minimal position or enhancer dependence in transgenic mice

Document Type

Journal Article

Publication Date



Journal of Biological Chemistry






In red blood cells ankyrin (ANK-1) provides the primary linkage between the erythrocyte membrane skeleton and the plasma membrane. We have previously demonstrated that a 271-bp 5'-flanking region of the ANK-1 gene has promoter activity in erythroid, but not non-erythroid, cell lines. To determine whether the ankyrin promoter could direct erythroid-specific expression in vivo, we analyzed transgenic mice containing the ankyrin promoter fused to the human (A)γ-globin gene. Sixteen of 17 lines expressed the transgene in erythroid cells indicating nearly position-independent expression. We also observed a significant correlation between the level of Ank/(A)γ-globin mRNA and transgene copy number. The level of Ank/(A)γ mRNA averaged 11% of mouse α-globin mRNA per gene copy at all developmental stages. The addition of the HS2 enhancer from the β-globin locus control region to the Ank/(A)γ-globin transgene resulted in Ank/(A)γ-globin mRNA expression in embryonic and fetal erythroid cells in six of eight lines but resulted in absent or dramatically reduced levels of Ank/ (A)γ-globin mRNA in adult erythroid cells in eight of eight transgenic lines. These data indicate that the minimal ankyrin promoter contains all sequences necessary and sufficient for erythroid-specific, copy number-dependent, position-independent expression of the human (A)γ-globin gene.

This document is currently not available here.