Regulation of cardiac beta 1-adrenergic receptor transcription during the developmental transition.
The beta(1)-adrenergic receptor (beta(1)AR) gene contains binding sites for myc/max proteins within a glucocorticoid response element. Transcriptional activation of the beta(1)AR is the result of cooperative binding between c-myc and the glucocorticoid receptor on the beta(1)AR promoter. The transcriptional regulation of both beta(1)AR and c-myc are developmentally regulated. We used transcription rate assays of nuclei isolated from fetal hearts to demonstrate a fivefold increase in the transcription rate of beta(1)AR vs. postnatal hearts (P < 0.01). This was associated with a fourfold increase in c-myc transcription. Transcription rate assays performed in a rat fibroblast cell line that overexpresses c-myc (myc(+/+)) showed similarly increased beta(1)AR expression compared with the wild-type cell line. Transient transfection experiments in the myc(+/+) cells demonstrated robust expression of beta(1)AR promoter constructs, which was abrogated by mutation of the myc/max binding site or by cotransfection with a c-myc antisense expression vector. These results suggest that the regulation of cardiac beta(1)AR transcription and the expression of c-myc are tightly integrated.
Women and Infants' Hospital of Rhode Island, Brown University School of Medicine, Providence 02905-2499, USA.
Rajan
R
Wadhawan
Yi-Tang
YT
Tseng
Joan
J
Stabila
Bethany
B
McGonnigal
Sumita
S
Sarkar
James
J
Padbury
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006321:Heart / Q000196:embryology*; D007700:Kinetics; D032342:Muscle Cells / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense; D011247:Pregnancy; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000096:biosynthesis* / Q000235:genetics*; D012756:Sheep; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D014162:Transfection
D020319:Oligodeoxyribonucleotides, Antisense; D016271:Proto-Oncogene Proteins c-myc; D018342:Receptors, Adrenergic, beta-1