CREM gene: use of alternative DNA-binding domains generates multiple antagonists of cAMP-induced transcription

Cell. 1991 Feb 22;64(4):739-49. doi: 10.1016/0092-8674(91)90503-q.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Northern
  • Blotting, Southern
  • Cell Line
  • Cyclic AMP / pharmacology*
  • Cyclic AMP Response Element Modulator
  • Cyclic AMP Response Element-Binding Protein
  • DNA / genetics
  • DNA / isolation & purification
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Library
  • Humans
  • Mice
  • Molecular Sequence Data
  • Oligonucleotide Probes
  • Pituitary Gland / metabolism
  • Placenta / metabolism
  • Plasmids
  • Polymerase Chain Reaction
  • Pregnancy
  • Protein Biosynthesis
  • RNA, Messenger / genetics
  • Repressor Proteins*
  • Restriction Mapping
  • Sequence Homology, Nucleic Acid
  • Transcription, Genetic* / drug effects
  • Transfection


  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • Oligonucleotide Probes
  • RNA, Messenger
  • Repressor Proteins
  • Cyclic AMP Response Element Modulator
  • DNA
  • Cyclic AMP

Associated data

  • GENBANK/M60285