Published in

Elsevier, Journal of Biological Chemistry, 48(273), p. 32200-32212, 1998

DOI: 10.1074/jbc.273.48.32200

Links

Tools

Export citation

Search in Google Scholar

Promoter Architecture, Cofactors, and Orphan Receptors Contribute to Cell-specific Activation of the Retinoic Acid Receptor β2 Promoter

Journal article published in 1998 by Gert E. Folkers ORCID, Bart van der Burg, Paul T. van der Saag
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

Full text: Download

Green circle
Preprint: archiving allowed
Green circle
Postprint: archiving allowed
Green circle
Published version: archiving allowed
Data provided by SHERPA/RoMEO

Abstract

Expression of retinoic acid receptor beta (RARbeta) is spatially and temporally restricted during embryonal development. Also during retinoic acid (RA)-dependent embryonal carcinoma (EC) cell differentiation, RARbeta expression is initially up-regulated, while in later phases of differentiation expression is down-regulated, by an unknown mechanism. To gain insight into the regulation of RARbeta, we studied the activity of the RARbeta2 promoter and mutants thereof in various cell lines. While the RARbeta2 promoter is activated by RA in a limited number of cell lines, synthetic RA-responsive reporters are activated in most cell types. We show that the expression levels of proteins that bind to the beta-retinoic acid response element (RAR/retinoid X receptors and orphan receptors) and also the differential expression of a number of coactivators modulate the RA response on both natural and synthetic reporters. We further show that cell type-specific activation of the RARbeta2 promoter is dependent on the promoter architecture including the spacing between retinoic acid response element and TATA-box and initiator sequence (betaINR). Mutation within these regions caused a decrease in the activity of this promoter in responsive EC cells, while an increase in activity in non-EC cell lines was observed. Cell-specific complexes were formed on the betaINR, suggesting that the betaINR contributes to cell-specific activation of the promoter. On this basis we propose that promoter context-dependent and more general RA response-determining mechanisms contribute to cell-specific RA-dependent activation of transcription.