Polarity-specific activities of retinoic acid receptors determined by a co-repressor

Nature. 1995 Oct 5;377(6548):451-4. doi: 10.1038/377451a0.


Retinoic acid receptors (RARs) and retinoid-X receptors (RXRs) activate or repress transcription by binding as heterodimers to DNA-response elements that generally consist of two direct repeat half-sites of consensus sequence AGGTCA. On response elements consisting of direct repeats spaced by five base pairs (DR + 5 elements), RAR/RXR heterodimers activate transcription in response to RAR-specific ligands, such as all-trans-retinoic acid (RA). In contrast, on elements consisting of direct repeats spaced by one base pair (DR + 1 elements), RAR/RXR heterodimers exhibit little or no response to activating ligands and repress RXR-dependent transcription. Here we show that ligand-dependent transactivation by RAR on DR + 5 elements requires the dissociation of a new nuclear receptor co-repressor, N-CoR, and recruitment of the putative co-activators p140 and p160. Surprisingly, on DR + 1 elements, N-CoR remains associated with RAR/RXR heterodimers even in the presence of RAR ligands, resulting in constitutive repression. These observations indicate that DNA-response elements can allosterically regulate RAR-co-repressor interactions to determine positive or negative regulation of gene expression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Allosteric Regulation
  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites
  • Cell Line
  • Humans
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Nuclear Proteins / metabolism*
  • Nuclear Receptor Co-Repressor 1
  • Receptors, Retinoic Acid / metabolism*
  • Regulatory Sequences, Nucleic Acid
  • Repressor Proteins / metabolism*
  • Retinoid X Receptors
  • Transcription Factors / metabolism
  • Transcriptional Activation*


  • NCOR1 protein, human
  • Nuclear Proteins
  • Nuclear Receptor Co-Repressor 1
  • Receptors, Retinoic Acid
  • Repressor Proteins
  • Retinoid X Receptors
  • Transcription Factors