Thyroid hormone regulates expression of a transfected human. alpha. -myosin heavy-chain fusion gene in fetal rat heart cells
- Univ. of Arizona College of Medicine, Tucson (USA)
- Albert Einstein College of Medicine, Bronx, NY (USA)
The rat {alpha}-myosin heavy-chain ({alpha}-MHC) gene is regulated by 3,5,3{prime}-triiodo-L-thyronine (T{sub 3}) in ventricular myocardium and is constitutively expressed in atrial tissue. Less is known about regulation of the human gene, but conservation of sequences in the 5{prime}-flanking region between the rat and human {alpha}-MHC genes suggests that the human gene may be regulated similarly. Accordingly, T{sub 3}-responsiveness and tissue-specific expression of human and rat {alpha}-MHC/chloramphenicol acetyltransferase fusion constructs have been compared in rat fetal heart cells, L{sub 6}E{sub 9} myoblasts and myotubes, 3T3 fibroblasts, and HeLa cells. Transient transfection assays revealed a complex series of cis-regulatory elements in the 5{prime}-flanking sequences in the human genes, including a basal promoter element with canonical TATAA and CAAT sequences, two positive regulatory element(s), and two negative regulatory-elements, which markedly diminished both constitutive and T{sub 3}-inducible activity. Interestingly, the human gene seemed to contain a proximal thyroid-hormone response element(s) not found in the rat gene. The authors propose that interactions among the thyroid hormone responsive elements and other cis-acting elements in the human {alpha}-MHC 5{prime}-flanking sequences may be sufficient to explain the characteristic features of expression of this gene in cardiac tissues.
- OSTI ID:
- 6941408
- 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. 87:1; ISSN 0027-8424; ISSN PNASA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
BODY
CARDIOVASCULAR SYSTEM
CELL CONSTITUENTS
CONNECTIVE TISSUE CELLS
DNA SEQUENCING
ENZYME ACTIVITY
ENZYMES
FIBROBLASTS
GENE REGULATION
GENES
GLOBULINS
HEART
HELA CELLS
HORMONES
MAMMALS
MAN
MUSCLES
MYOCARDIUM
MYOSIN
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PLASMIDS
PRIMATES
PROTEINS
RATS
RODENTS
SOMATIC CELLS
STRUCTURAL CHEMICAL ANALYSIS
THYROID HORMONES
TRANSFERASES
TRIIODOTHYRONINE
VERTEBRATES