Regulated expression of genes inserted at the human chromosomal. beta. -globin locus by homologous recombination
- Albert Einstein College of Medicine, Bronx, NY (USA)
The authors have examined the effect of the site of integration on the expression of cloned genes introduced into cultured erythroid cells. Smithies et al. reported the targeted integration of DNA into the human {beta}-globin locus on chromosome 11 in a mouse erythroleukemia-human cell hybrid. These hybrid cells can undergo erythroid differentiation leading to greatly increased mouse and human {beta}-globin synthesis. By transfection of these hybrid cells with a plasmid carrying a modified human {beta}-globin gene and a foreign gene composed of the coding sequence of the bacterial neomycin-resistance gene linked to simian virus 40 transcription signals (SVneo), cells were obtained in which the two genes are integrated at the {beta}-globin locus on human chromosome 11 or at random sites. When they examined the response of the integrated genes to cell differentation, they found that the genes inserted at the {beta}-globin locus were induced during differentiation, whereas randomly positioned copies were not induced. Even the foreign SVneo gene was inducible when it had been integrated at the {beta}-globin locus. The results show that genes introduced at the {beta}-globin locus acquire some of the regulatory properties of globin genes during erythroid differentiation.
- OSTI ID:
- 5404759
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 85:11; ISSN PNASA; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CELL DIFFERENTIATION
CHROMOSOMES
DAYS LIVING RADIOISOTOPES
GENE RECOMBINATION
GENE REGULATION
GLOBIN
HETEROCHROMOSOMES
HYBRIDIZATION
ISOTOPES
LIGHT NUCLEI
MAMMALS
MAN
MESSENGER-RNA
MICE
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PRIMATES
RADIOISOTOPES
RNA
RODENTS
TRANSCRIPTION
TUMOR CELLS
VERTEBRATES