Glucocorticoid regulation of transcription at an amplified, episomal promoter
The mouse mammary tumor virus long terminal repeat (MMTV LTR) has been introduced into cultured murine cells, using the 69% transforming fragment of bovine papiloma virus type 1 (BVP). Transformed cells contain up to 200 copies of the chimeric molecules per diploid genome. The restriction endonuclease map of the acquired recombinants, as well as the physical structure of the DNA, indicates that the LTR-BVP molecules present in these cells occur exclusively as unintegrated, extrachromosomal episome. When a 72-base pair direct repeat ''enhancer'' element (derived from the Harvey sarcoma retrovirus) was included in the MMTV LTR-BPV chimeric plasmids, DNA acquired through transfection, with a single exception, was integrated or rearranged or both. Two approaches showed that the MMTV LTR present in the episomal state was capable of supporting glucocorticoid hormone-regulated transcription. The authors have therefore demonstrated the hormone response for the first time in a totally defined primary sequence environment. Significant differences both in the basal level of MMTV-initiated transcription and in the extend of glucocorticoid induction were observed in individual cell lines with similar episomal copy numbers. These phenotypic variations suggest that epigenetic structure is an important component of the mechanism of regulation.
- Research Organization:
- Lab. of Tumor Virus Genetics, National Cancer Institute, Bethesda, MD 20205
- OSTI ID:
- 5823343
- Journal Information:
- Mol. Cell. Biol.; (United States), Vol. 3:11
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ENDONUCLEASES
ENZYME INDUCTION
GENETIC MAPPING
GLUCOCORTICOIDS
BIOLOGICAL FUNCTIONS
BIOSYNTHESIS
MAMMARY GLANDS
NEOPLASMS
ONCOGENES
GENE AMPLIFICATION
GENE REGULATION
RECOMBINANT DNA
STRUCTURE-ACTIVITY RELATIONSHIPS
CATTLE
CELL CULTURES
DIPLOIDY
GENETIC ENGINEERING
IN VIVO
MICE
ONCOGENIC TRANSFORMATIONS
ONCOGENIC VIRUSES
PLASMIDS
TRANSCRIPTION
TRANSPOSONS
ADRENAL HORMONES
ANIMALS
BODY
CELL CONSTITUENTS
CELL TRANSFORMATIONS
CORTICOSTEROIDS
DISEASES
DNA
DNA-ASE
DOMESTIC ANIMALS
ENZYMES
ESTERASES
FUNCTIONS
GENES
GLANDS
HYDROLASES
HYDROXY COMPOUNDS
KETONES
MAMMALS
MAPPING
MICROORGANISMS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PARASITES
PHOSPHODIESTERASES
PLOIDY
PREGNANES
RODENTS
RUMINANTS
STEROIDS
SYNTHESIS
VERTEBRATES
VIRUSES
550400* - Genetics
550200 - Biochemistry
550900 - Pathology