Analysis of the human alpha-globin gene cluster in transgenic mice.
- 1 December 1993
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 90 (23), 11262-11266
- https://doi.org/10.1073/pnas.90.23.11262
Abstract
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.Keywords
This publication has 32 references indexed in Scilit:
- A single point mutation is the cause of the Greek form of hereditary persistence of fetal haemoglobinNature, 1992
- A major positive regulatory region located far upstream of the human alpha-globin gene locus.Genes & Development, 1990
- A dominant control region from the human β-globin locus conferring integration site-independent gene expressionNature, 1989
- DNA Sequences Regulating Human Globin Gene Transcription in Nondeletional Hereditary Persistence of Fetal HemoglobinHemoglobin, 1989
- Position-independent, high-level expression of the human β-globin gene in transgenic miceCell, 1987
- Recombination at the human α-globin gene cluster: Sequence features and topological constraintsCell, 1987
- Rapid reprogramming of globin gene expression in transient heterokaryonsCell, 1986
- Identification of two distinct regulatory regions adjacent to the human β-interferon geneCell, 1983
- The chromosomal arrangement of human α-like globin genes: Sequence homology and α-globin gene deletionsCell, 1980