Proximal promoter elements of the human zeta-globin gene confer embryonic-specific expression on a linked reporter gene in transgenic mice.

Journal article

We have investigated the transcriptional regulation of the human embryonic zeta-globin gene promoter. First, we examined the effect that deletion of sequences 5' to zeta-globin's CCAAT box have on zeta-promoter activity in erythroid cell lines. Deletions of sequences between -116 and -556 (cap = 0) had little effect while further deletion to -84 reduced zeta-promoter activity by only 2-3-fold in both transiently and stably transfected erythroid cells. Constructs containing 67, 84 and 556 bp of zeta-globin 5' flanking region linked to a beta-galactosidase reporter gene (lacZ) and hypersensitive site -40 (HS-40) of the human alpha-globin gene cluster were then employed for the generation of transgenic mice. LacZ expression from all constructs, including a 67 bp zeta-globin promoter, was erythroid-specific and most active between 8.5 and 10.5 days post-fertilisation. By 16.5 days gestation, lacZ expression dropped 40-100-fold. These results suggest that embryonic-specific activation of the human zeta-globin promoter is conferred by a 67 bp zeta-promoter fragment containing only a CCAAT and TATA box.

Authors: Pondel, MD; Sharpe, J; Clark, S; Pearson, L; Wood, W

• Publication status: Published
• Journal: Nucleic acids research
• Volume: 24
• Issue: 21
• Pages: 4158-4164
• Publication date: 1996-11-01
• DOI: 10.1093/nar/24.21.4158
• EISSN: 1362-4962
• ISSN: 0305-1048
• Language: English
• Keywords: Erythrocytes; Transfection; Fetus; Gene Expression Regulation, Developmental; Mice; Genes, Reporter; Male; Promoter Regions, Genetic; Animals; Female; Liver; Mice, Inbred C57BL; Lac Operon; Cell Line; Mice, Inbred CBA; Globins; Embryo, Mammalian; Humans; Mice, Transgenic