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Retinoic acid receptor isoform RARγ 1: an antagonist of the transactivation of the RARβ RARE in epithelial cell lines and normal human keratinocytes

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Abstract

The diversity of isoforms of retinoic acid (RA) receptors (RARs) and of DNA sequences of retinoic acid-responsive elements (RAREs) suggests the existence of selectivities in the RAR/RARE recognition or in the subsequent gene modulation. Such selectivities might be particularly important for RAREs involved in positive feedback, eg. the RARβ RARE. In the present work we found that in several epithelial cell lines, reporter constructs containing the RARβ RARE linked to the HSV-tk promoter were transactivated in the presence of RA by endogenous RARs and co-transfected RARα1 and RARβ2 isoforms, but not by RARγ1. On the contrary, this latter isoform behaved towards the RARβ RARE as an inhibitor of the transactivation produced by endogenous RARs and by cotransfected RARα1 and RARβ2. RARγ1 also behaved as an antagonist of the transactivation produced by cotransfected RXRα. The natural RARβ gene promoter or RARβ RARE tk constructs were not activated by the endogenous receptors of normal human keratinocytes (NHK), which are known to contain predominantly RARγ1. It was, however, possible to activate to a certain extent RARβ RARE-reporter constructs in NHK by co-transfecting RARα1, RARβ2 or RXRα. The antagonist behavior of RARγ1 towards the RARβ RARE may explain why in certain cell types such as keratinocytes, RARβ is neither expressed nor induced by RA.

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Abbreviations

DMEM:

Dulbecco's modified Eagle medium

DMSO:

dimethyl sulfoxide

FCS:

fetal calf serum

MEM:

minimal Eagle medium

NHK:

normal human keratinocyte

RA:

retinoic acid

RAR:

retinoic acid receptor

RARE:

retinoic acid responsive element

TRE:

thyroid responsive element

VDRE:

vitamin D response element

RXR:

retinoid X receptor

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Author notes

  1. C. Clusel

    Present address: GENSET, 1 Passage E. Delaunay, 75011, Paris, France

Authors and Affiliations

  1. Cell Biology Department, Centre International de Recherches Dermatologiques (CIRD Galderma), Sophia Antipolis, F-06565, Valbonne, France

    C. Miquel, C. Clusel, A. Semat, C. Gerst & M. Darmon

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Miquel, C., Clusel, C., Semat, A. et al. Retinoic acid receptor isoform RARγ 1: an antagonist of the transactivation of the RARβ RARE in epithelial cell lines and normal human keratinocytes. Mol Biol Rep 17, 35–45 (1993). https://doi.org/10.1007/BF01006398

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