Promoter context- and response element-dependent specificity of the transcriptional activation and modulating functions of retinoic acid receptors.
Using several naturally occurring and synthetic retinoic acid (RA)-responsive reporter genes, we show that the patterns of transcriptional activation by various retinoic acid receptor (RAR) and retinoid X receptor (RXR) forms vary according to the nature of the RA response element and the context of the stimulated promoter. We demonstrate the presence of autonomous, ligand-inducible, and promoter context-dependent transactivation functions (AF-2s) located in the C-terminal region of all RARs and RXRs. In addition, promoter context-specific modulating transactivation functions are associated with the N-terminal A and B regions of RARs and RXRs. We also show that these transactivation and modulating functions exhibit response-element specificity. The modulating functions display a marked specificity in their cooperation with the AF-2 transactivation functions, cooperation that depends on the receptor origin of the modulating and transactivation functions and the promoter context of the RA-responsive gene, thus accounting for the specific transactivation properties of RAR and RXR types.
Nagpal
S
S
Laboratoire de Génétique Moléculaire des Eucaryotes, Centre National de la Recherche Scientifique, Faculté de Médecine, Strasbourg, France.
Saunders
M
M
Kastner
P
P
Durand
B
B
Nakshatri
H
H
Chambon
P
P
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000502:physiology*; D002460:Cell Line; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000502:physiology*; D018168:Receptors, Retinoic Acid; D012045:Regulatory Sequences, Nucleic Acid; D047488:Retinoid X Receptors; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation; D014212:Tretinoin
D002352:Carrier Proteins; D011956:Receptors, Cell Surface; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin