Author:
Strouboulis J,Dillon N,Grosveld F
Abstract
We have used a linker-based ligation strategy to combine two 35-kb cosmid inserts from the human beta-globin locus into one linear fragment containing the entire locus. This 70-kb fragment was introduced into transgenic mice by microinjection of fertilized eggs. Southern blot analysis showed that a single complete transgene locus can be introduced into the germ line with high efficiency. Analysis of the expression patterns of the locus during development shows that the epsilon-globin gene behaves as a purely embryonic gene, the gamma-globin gene as an embryonic and early fetal gene, and the beta-globin gene as a fetal adult gene. Quantitation of expression showed that the levels of transcription of the epsilon- and gamma-globin genes are reversed relative to their mouse homologs but that the total output of the human and mouse loci is constant during development. These results suggest that multiple changes in DNA sequences and transcription factor balance must have occurred for the human gamma-globin gene to have evolved into a fetal gene.
Publisher
Cold Spring Harbor Laboratory
Subject
Developmental Biology,Genetics
Reference23 articles.
1. A single point mutation is the cause of the Greek form of hereditary persistence of fetal haemoglobin
2. The molecular genetics of human hemoglobin.;Prog. Nucleic Acid Res. Mol. Biol.,1984
3. Human γ-globin genes silenced independently of other genes in the β-globin locus
4. Dillon, N., D. Talbot, S. Philipsen, O. Hanscombe, P. Fraser, S. Pruzina, M. Lindenbaum, and F. Grosveld. 1991. The regulation of the human β-globin locus. Gene expression and its control. In Genome analysis (ed. K.E. Davies and S.M. Tilghman), Vol. 2, pp. 99â118. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York.
5. Gamma delta beta-thalassemia due to a de novo mutation deleting the 5' beta-globin gene activation-region hypersensitive sites.
Cited by
197 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献