CREM gene: use of alternative DNA-binding domains generates multiple antagonists of cAMP-induced transcription.
We isolated a gene from a mouse pituitary cDNA library that encodes a protein highly homologous to nuclear factor CREB, an activator of cAMP-responsive promoter elements (CREs). We demonstrate that while CREB is expressed uniformly in several cell types, this gene, termed CREM, shows cell-specific expression. CREM has a remarkable organization, since down-stream of the stop codon there is a second, out-of-frame DNA-binding domain. Using PCR and RNAase protection analysis, we have identified three mRNA isoforms that appear to be obtained by differential cell-specific splicing. Sequencing of the isoforms demonstrated alternative usage of the two DNA-binding domains. CREM proteins reveal the same efficiency and specificity of binding to CRE sequences as CREB, but in contrast to CREB, CREM acts as a down-regulator of cAMP-induced transcription.
Foulkes
N S
NS
Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Faculté de Médecine, Strasbourg, France.
Borrelli
E
E
Sassone-Corsi
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology*; D051786:Cyclic AMP Response Element Modulator; D017362:Cyclic AMP Response Element-Binding Protein; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015723:Gene Library; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010902:Pituitary Gland / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D012097:Repressor Proteins; D051786:Cyclic AMP Response Element Modulator; D004247:DNA; D000242:Cyclic AMP