H-2RIIBP (RXRβ) heterodimerization provides a mechanism for combinatorial diversity in the regulation of retinoic acid and thyroid hormone responsive genes

M. S. Marks, P. L. Hallenbeck, T. Nagata, J. H. Segars, E. Appella, V. M. Nikodem, K. Ozato

Research output: Contribution to journalArticlepeer-review

Abstract

H-2RIIBP (RXRβ) is a member of the nuclear hormone receptor superfamily that activates transcription of MHC class I genes in response to retinoic acid (RA). Using chemical cross-linking, co-immunoprecipitation, gel mobility shift and streptavidin-biotin DNA precipitation assays, we show that H-2RIIBP formed heterodimers with thyroid hormone (T3) and RA receptors (T3Rα and RARα). H-2RIIBP heterodimer formation required a conserved sub-domain of its C-terminal region, occurred independently of target DNA and was much more efficient than either T3Rα/RARα heterodimer or H-2RIIBP homodimer formation. Heterodimers displayed enhanced binding to target DNA elements and contacted DNA in a manner distinct from that of homodimers. A functional role for heterodimers in vivo was demonstrated by synergistic enhancement of MHC class I transcription following co-transfection of H-2RIIBP with T3Rα or RARα. We provide biochemical evidence that H-2RIIBP formed heterodimers with several naturally occurring nuclear proteins. The results suggest that H-2RIIBP, by virtue of its ability to heterodimerize, enhances combinatorial diversity and versatility in gene regulation mediated by nuclear hormone receptors.

Original languageEnglish (US)
Pages (from-to)1419-1435
Number of pages17
JournalEMBO Journal
Volume11
Issue number4
DOIs
StatePublished - 1992
Externally publishedYes

Keywords

  • Dimerization
  • Gene regulation
  • Hormone receptors
  • Retinoic acid
  • Thyroid hormone

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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