Inducibility and negative autoregulation of CREM: an alternative promoter directs the expression of ICER, an early response repressor.
cAMP-responsive element modulator (CREM) expression is tissue specific and developmentally regulated. Here we report that CREM is unique within the family of cAMP-responsive promoter element (CRE)-binding factors since it is inducible by activation of the cAMP signaling pathway. The kinetic of expression is characteristic of an early response gene. The induction is transient and cell specific, does not involve increased transcript stability, and does not require protein synthesis. Significantly, the subsequent decline in CREM expression requires de novo protein synthesis. The induced transcript encodes a novel repressor, inducible cAMP early repressor (ICER), and is generated from an alternative intronic promoter. A cluster of four CREs in this promoter directs cAMP inducibility. ICER binds to these elements and thereby represses the activity of its own promoter, thus constituting a negative autoregulatory loop.
Molina
C A
CA
Laboratoire de Génétique Moléculaire des Eucaryotes, Institut National de la Santé et de la Recherche Médicale, Strasbourg, France.
Foulkes
N S
NS
Lalli
E
E
Sassone-Corsi
P
P
D000262:Adenylyl Cyclases / Q000502:physiology; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000502:physiology; D051786:Cyclic AMP Response Element Modulator; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011953:Receptors, Cyclic AMP / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics*; D015398:Signal Transduction; D013997:Time Factors
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011953:Receptors, Cyclic AMP; D012097:Repressor Proteins; D051786:Cyclic AMP Response Element Modulator; D000242:Cyclic AMP; D000262:Adenylyl Cyclases