RARs and RXRs: Evidence for two autonomous transactivation functions (AF-1 and AF-2) and heterodimerization in vivo

Sunil Nagpal, Sylvie Friant, Harikrishna Nakshatri, Pierre Chambon

Research output: Contribution to journalArticle

257 Citations (Scopus)

Abstract

We have previously reported that the AB regions of retinoic acid receptors (RARs and RXRs) contain a transcriptional activation function capable of modulating the activity of the ligand-dependent activation function present in the C-terminal DE regions of these receptors. However, we could not demonstrate that these AB regions possess an autonomous activation function similar to the AF-1s found in the AB regions of steroid hormone receptors. Using the mouse CRBPII promoter as a reporter gene, we now report that the AB regions of RARα, β and γ, as well as those of RXRα and γ, contain an autonomous, ligand-independent activation function, AF-1, which can efficiently synergize with AF-2s. Moreover, AF-1s account for the ligand-independent, constitutive activation of transcription by RXRα and γ. We also show that RARs and RXRs preferentially heterodimerize in solution in cultured cells in vivo, through the dimerization interface present in their E region, irrespective of the presence of all-trans or 9-cis retinoic acid. Furthermore, our results indicate that homodimeric interactions are not observed in cultured cells in vivo under conditions where heterodimeric interactions readily occur, which is in agreement with previous observations showing the preferential binding of RAR-RXR heterodimers to RA response elements in vitro.

Original languageEnglish (US)
Pages (from-to)2349-2360
Number of pages12
JournalEMBO Journal
Volume12
Issue number6
StatePublished - 1993
Externally publishedYes

Fingerprint

Furylfuramide
Transcriptional Activation
Chemical activation
Ligands
Cultured Cells
Retinoic Acid Receptors
Steroid Receptors
Dimerization
Response Elements
Reporter Genes
Steroid hormones
E region
Cells
Hormones
Transcription
Thermodynamic properties
Genes

Keywords

  • AF-1
  • AF-2
  • Autonomous transactivation functions
  • Heterodimerization
  • Retinoic acid receptors

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

RARs and RXRs : Evidence for two autonomous transactivation functions (AF-1 and AF-2) and heterodimerization in vivo. / Nagpal, Sunil; Friant, Sylvie; Nakshatri, Harikrishna; Chambon, Pierre.

In: EMBO Journal, Vol. 12, No. 6, 1993, p. 2349-2360.

Research output: Contribution to journalArticle

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