Retinoic acid induction of major histocompatibility complex class I genes in NTera-2 embryonal carcinoma cells involves induction of NF-κB (p50-p65) and retinoic acid receptor β-retinoid X receptor β heterodimers

J. H. Segars, T. Nagata, V. Bours, J. A. Medin, G. Franzoso, J. C.G. Blanco, P. D. Drew, K. G. Becker, J. An, T. Tang, D. A. Stephany, B. Neel, U. Siebenlist, K. Ozato

Research output: Contribution to journalArticlepeer-review

Abstract

Retinoic acid (RA) treatment of human embryonal carcinoma (EC) NTera-2 (NT2) cells induces expression of major histocompatibility complex (MHC) class I and β-2 microglobulin surface molecules. We found that this induction was accompanied by increased levels of MHC class I mRNA, which was attributable to the activation of the two conserved upstream enhancers, region I (NF-κB like) and region II. This activation coincided with the induction of nuclear factor binding activities specific for the two enhancers. Region I binding activity was not present in undifferentiated NT2 cells, but binding of an NF-κB heterodimer, p50-p65, was induced following RA treatment. The p50-p65 heterodimer was produced as a result of de novo induction of p50 and p65 mRNAs. Region II binding activity was present in undifferentiated cells at low levels but was greatly augmented by RA treatment because of activation of a nuclear hormone receptor heterodimer composed of the retinoid X receptor (RXRβ) and the RA receptor (RARβ). The RXRβ-RARβ heterodimer also bound RA responsive elements present in other genes which are likely to be involved in RA triggering of EC cell differentiation. Furthermore, transfection of p50 and p65 into undifferentiated NT2 cells synergistically activated region I-dependent MHC class I reporter activity. A similar increase in MHC class I reporter activity was demonstrated by cotransfection of RXRβ and RARβ. These data show that following RA treatment, heterodimers of two transcription factor families are induced to bind to the MHC enhancers, which at least partly accounts for RA induction of MHC class I expression in NT2 EC cells.

Original languageEnglish (US)
Pages (from-to)6157-6169
Number of pages13
JournalMolecular and cellular biology
Volume13
Issue number10
DOIs
StatePublished - 1993
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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