Analysis of the human [alpha]-globin gene cluster in transgenic mice
- Univ. of Oxford, Oxford (United Kingdom)
- Royal Veterinary College, Royal College Street, London (United Kingdom)
- Univ. of Sydney, Sydney (Australia)
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, the authors 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.
- OSTI ID:
- 7182528
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 90:22; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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