Positive and negative regulation of gene transcription by a retinoic acid-thyroid hormone receptor heterodimer.
We present evidence that the human thyroid hormone receptor forms a heterodimer with the human retinoic acid receptor. This interaction results in a cooperative increase in binding of the alpha retinoic acid receptor to a subset of thyroid hormone response elements. Mutations within the DNA binding domain or near the C-terminus abolish either receptor's ability to interact cooperatively on these elements. The thyroid hormone-retinoic acid receptor heterodimer exhibits novel transcriptional properties in that coexpression of both receptors at low levels in Green monkey kidney (CV1) cells results in a positive transcriptional effect on promoters containing a palindromic thyroid hormone response element, but has a surprisingly negative effect on a thyroid hormone response element derived from the alpha myosin heavy chain gene. These results suggest that by forming heterodimers, more elab-orate control of transcription can be achieved by creating receptor combinations with differing activities.
Glass
C K
CK
Eukaryotic Regulatory Biology Program Center for Molecular Genetics, University of California, San Diego, La Jolla 92093-0613.
Lipkin
S M
SM
Devary
O V
OV
Rosenfeld
M G
MG
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002460:Cell Line; D002872:Chromosome Deletion; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D005796:Genes; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D011485:Protein Binding; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D014158:Transcription, Genetic; D014162:Transfection; D014212:Tretinoin / Q000378:metabolism
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D014212:Tretinoin; D004247:DNA