Inhibition of ligand induced promoter occupancy in vivo by a dominant negative RXR

Jorge C G Blanco, Anup Dey, Mark Leid, Saverio Minucci, Byung Kiu Park, Peter W. Jurutka, Mark R Haussler, Keiko Ozato

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: Retinoid X receptors (RXRs) heterodimerize with other nuclear hormone receptors and control ligand mediated transcription. To address how RXRs function as heterodimers, we investigated activities of truncated RXRα and RXRβ that lack ≈ 20 conserved C-terminal amino acids. Results: The truncated RXRs formed heterodimers and bound to respective DNA elements in vitro. By transient reporter assays we found that these RXRs act as dominant negative receptors and inhibit ligand dependent transcription by the retinoic acid receptor (RAR) and vitamin D receptor. P19 embryonal carcinoma cells stably expressing the truncated RXRβ (termed ΔC2) were deficient in activating the endogenous RARβ gene and an RA responsive reporter. To study the dominant negative activity of ΔC2 further, genoniic footprinting analysis was performed for the RARβ2 promoter. In control P19 clones, the RA responsive element (RARE) and other elements in the promoter were protected after RA treatment. However, in ΔC2 clones RA-induced protection was markedly inhibited at all elements. Conclusions: These results indicate that the C-terminal region of RXR is required for full RARE occupancy in vivo, a RA dependent process that leads to the recruitment of other factors to the promoter and the subsequent transcriptional activation. Thus, RXRs play an integral role in ligand dependent transcription.

Original languageEnglish (US)
Pages (from-to)209-221
Number of pages13
JournalGenes to Cells
Volume1
Issue number2
StatePublished - 1996
Externally publishedYes

Fingerprint

Retinoid X Receptors
Ligands
Retinoic Acid Receptors
Clone Cells
Embryonal Carcinoma Stem Cells
Calcitriol Receptors
Cytoplasmic and Nuclear Receptors
Transcriptional Activation
Amino Acids

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

Blanco, J. C. G., Dey, A., Leid, M., Minucci, S., Park, B. K., Jurutka, P. W., ... Ozato, K. (1996). Inhibition of ligand induced promoter occupancy in vivo by a dominant negative RXR. Genes to Cells, 1(2), 209-221.

Inhibition of ligand induced promoter occupancy in vivo by a dominant negative RXR. / Blanco, Jorge C G; Dey, Anup; Leid, Mark; Minucci, Saverio; Park, Byung Kiu; Jurutka, Peter W.; Haussler, Mark R; Ozato, Keiko.

In: Genes to Cells, Vol. 1, No. 2, 1996, p. 209-221.

Research output: Contribution to journalArticle

Blanco, JCG, Dey, A, Leid, M, Minucci, S, Park, BK, Jurutka, PW, Haussler, MR & Ozato, K 1996, 'Inhibition of ligand induced promoter occupancy in vivo by a dominant negative RXR', Genes to Cells, vol. 1, no. 2, pp. 209-221.
Blanco JCG, Dey A, Leid M, Minucci S, Park BK, Jurutka PW et al. Inhibition of ligand induced promoter occupancy in vivo by a dominant negative RXR. Genes to Cells. 1996;1(2):209-221.
Blanco, Jorge C G ; Dey, Anup ; Leid, Mark ; Minucci, Saverio ; Park, Byung Kiu ; Jurutka, Peter W. ; Haussler, Mark R ; Ozato, Keiko. / Inhibition of ligand induced promoter occupancy in vivo by a dominant negative RXR. In: Genes to Cells. 1996 ; Vol. 1, No. 2. pp. 209-221.
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