All-trans and 9-cis retinoic acid induction of CRABPII transcription is mediated by RAR-RXR heterodimers bound to DR1 and DR2 repeated motifs

Cell. 1992 Oct 2;71(1):73-85. doi: 10.1016/0092-8674(92)90267-g.


Two cooperating retinoic acid response elements (RAREs) in the cellular retinoic acid-binding protein II (CRABPII) gene mediate differential transcriptional transactivation by retinoic acid receptors (RARs) and retinoid X receptors (RXRs) in P19 embryonal carcinoma cells. RARE1 and RARE2 are direct repeats (DR) of two motifs separated by 2 bp (DR2) and 1 bp (DR1), respectively, and bind RAR-RXR heterodimers more efficiently than homodimers. Using all-trans and 9-cis RA, which differentially activate RARs and RXRs, and RAR and RXR dominant-negative mutants, RAR-RXR heterodimers bound to RARE1 and RARE2 are shown to be responsible for CRABPII promoter transactivation, arguing against a unique DR spacing specifying recognition by RARs. Within heterodimers, RAR and RXR independently and differentially transactivate, depending on the specific RARE. Consistent with these results, 9-cis RA increases CRABPII mRNA levels more efficiently than all-trans RA. In contrast, all-trans and 9-cis RA have identical effects on induction of RAR beta 2 transcripts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Blotting, Northern
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Gene Expression Regulation / drug effects*
  • HeLa Cells
  • Humans
  • Macromolecular Substances
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism
  • Promoter Regions, Genetic / genetics
  • Receptors, Cell Surface / metabolism*
  • Receptors, Retinoic Acid
  • Recombinant Fusion Proteins / genetics
  • Repetitive Sequences, Nucleic Acid / genetics
  • Retinoid X Receptors
  • Transcription Factors*
  • Transcription, Genetic / genetics
  • Tretinoin / pharmacology*


  • Carrier Proteins
  • Macromolecular Substances
  • Nuclear Proteins
  • Receptors, Cell Surface
  • Receptors, Retinoic Acid
  • Recombinant Fusion Proteins
  • Retinoid X Receptors
  • Transcription Factors
  • Tretinoin

Associated data

  • GENBANK/L01528
  • GENBANK/L04285
  • GENBANK/S47136
  • GENBANK/S47137
  • GENBANK/S47164
  • GENBANK/S47165
  • GENBANK/S47166
  • GENBANK/S47167
  • GENBANK/S47168
  • GENBANK/S72771