Journal of Biological Chemistry
Volume 286, Issue 38, 23 September 2011, Pages 33322-33334
Journal home page for Journal of Biological Chemistry

Gene Regulation
Genome-wide in Silico Identification of New Conserved and Functional Retinoic Acid Receptor Response Elements (Direct Repeats Separated by 5 bp)

https://doi.org/10.1074/jbc.M111.263681Get rights and content
Under a Creative Commons license
open access

The nuclear retinoic acid receptors interact with specific retinoic acid (RA) response elements (RAREs) located in the promoters of target genes to orchestrate transcriptional networks involved in cell growth and differentiation. Here we describe a genome-wide in silico analysis of consensus DR5 RAREs based on the recurrent RGKTSA motifs. More than 15,000 DR5 RAREs were identified and analyzed for their localization and conservation in vertebrates. We selected 138 elements located ±10 kb from transcription start sites and gene ends and conserved across more than 6 species. We also validated the functionality of these RAREs by analyzing their ability to bind retinoic acid receptors (ChIP sequencing experiments) as well as the RA regulation of the corresponding genes (RNA sequencing and quantitative real time PCR experiments). Such a strategy provided a global set of high confidence RAREs expanding the known experimentally validated RAREs repertoire associated to a series of new genes involved in cell signaling, development, and tumor suppression. Finally, the present work provides a valuable knowledge base for the analysis of a wider range of RA-target genes in different species.

Computer Modeling
Nuclear Receptors
Retinoid
Transcription Promoter
Transcription Target Genes
Nuclear Retinoic Acid Receptors
Response Elements

Cited by (0)

The on-line version of this article (available at http://www.jbc.org) contains supplemental Tables S1–S5.

This work was supported by funds from CNRS, INSERM, the Association pour la Recherche sur le Cancer (ARC 3169), the Agence Nationale pour la Recherche (ANR-05-BLAN-0390-02 and ANR-09-BLAN-0127-01), the Fondation pour la Recherche Médicale (DEQ20090515423), and the Institut National du Cancer (INCa-PLO7-96099 and PL09-194).

1

Supported by the Association pour la Recherche sur le Cancer (ARC). Present address: Laboratory for Prenatal Medicine, Dept. of Biomedicine, University Hospital Basel, 4031 Basel, Switzerland.

2

Supported by the Ministère de l'Enseignement Supérieur et de la Recherche.