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Two 3' sequences direct adult erythroid-specific expression of human. beta. -globin genes in transgenic mice

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
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Previous experiments have demonstrated that the human ..beta..-globin gene is correctly regulated in transgenic mice. The ..beta..-globin gene is not expressed in yolk sac-derived erythroid cells in early embryonic development but is expressed concomitantly with the adult mouse ..beta..-globin genes in 14- to 16-day fetal liver and adult reticulocytes. In an attempt to localize sequences that direct erythroid-specific expression, fragments of the human ..beta..-globin gene were inserted in the opposite orientation 200 base pairs (bp) upstream of an intact human /sup A/..gamma.. marker gene, which is not expressed on its own in mouse fetal liver. In the experiments reported here, two ..beta..-globin 3' sequences activated the marker gene specifically in fetal liver. One sequence is located in a 250-bp Pst I fragment 550-800 bp downstream from the poly(A) site; the other is located near an EcoRI site in the third exon. These two sequences are active individually, and their combined effect is greater than their effects alone. ..beta..-Globin 5' sequences from -815 to -50 were also analyzed for activity in this assay. The 5' sequences did not activate the marker gene when tested alone but did stimulate expression that was already directed to adult erythroid tissue by the two 3' sequences. These results suggest that three separate sequences are involved in human ..beta..-globin gene regulation. The two 3' sequences act as adult erythroid enhancers and the 5' sequence stimulates expressions that is already determined to be erythroid specific.
Research Organization:
Univ. of Pennsylvania, Philadelphia (USA)
OSTI ID:
7027177
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:20; ISSN PNASA
Country of Publication:
United States
Language:
English

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Related Subjects

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59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
ADULTS
AGE GROUPS
ANIMALS
ATP
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DNA SEQUENCING
GENE REGULATION
GLANDS
GLOBIN
ISOTOPES
LIGHT NUCLEI
LIVER
MAMMALS
MAN
MESSENGER-RNA
MICE
NUCLEI
NUCLEIC ACIDS
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PRIMATES
PROTEINS
RADIOISOTOPES
RNA
RODENTS
STRUCTURAL CHEMICAL ANALYSIS
VERTEBRATES