Negative regulation of the rat Na-K-ATPase alpha 3-subunit gene promoter by thyroid hormone.
Na-K-ATPase alpha 3-subunit mRNA levels are both positively and negatively controlled by thyroid hormone [3,5,3'triiodothyronine (T3)] in primary cultures of neonatal rat cardiac myocytes. In this study, transient transfection analysis indicated that two regions of the rat alpha 3 gene between nucleotides -116 and -6 and -6 and +80 conferred T3-mediated inhibition of reporter gene expression. Electrophoretic mobility shift assays showed specific binding of T3 receptor monomers and T3 receptor-retinoid X receptor heterodimers at each alpha 3 gene negative T3-response region. The alpha 3 gene region from -116 to -6 base pairs also mediates repression in response to retinoic acid (RA) and binds RA receptor. In the absence of ligand, reporter gene expression driven by the -116 to -6-base pair region is repressed with cotransfection of T3 receptor, whereas it is unaffected by overexpression of RA receptor. These data demonstrate that the proximal promoter of the rat Na-K-ATPase alpha 3 gene contains sequence motifs that mediate repression of alpha 3 gene transcription in response to either T3 or RA in neonatal rat cardiac myocytes.
He
H
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Department of Biochemistry, State University of New York Health Science Center at Brooklyn 11203, USA.
Chin
S
S
Zhuang
K
K
Hartong
R
R
Apriletti
J
J
Gick
G
G
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D019281:Dimerization; D015971:Gene Expression Regulation, Enzymologic; D008156:Luciferases / Q000096:biosynthesis; D046911:Macromolecular Substances; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D047488:Retinoid X Receptors; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D014157:Transcription Factors / Q000096:biosynthesis; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology*
D046911:Macromolecular Substances; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014284:Triiodothyronine; D014212:Tretinoin; D008156:Luciferases; D000254:Sodium-Potassium-Exchanging ATPase