Bibliographic Details
| Title: |
The elongation complex components BRD4 and MLLT3/AF9 are transcriptional coactivators of nuclear retinoid receptors. |
| Authors: |
Sébastien Flajollet, Christophe Rachez, Maheul Ploton, Céline Schulz, Rozenn Gallais, Raphaël Métivier, Michal Pawlak, Aymeric Leray, Al Amine Issulahi, Laurent Héliot, Bart Staels, Gilles Salbert, Philippe Lefebvre |
| Source: |
PLoS ONE, Vol 8, Iss 6, p e64880 (2013) |
| Publisher Information: |
Public Library of Science (PLoS), 2013. |
| Publication Year: |
2013 |
| Collection: |
LCC:Medicine
LCC:Science |
| Subject Terms: |
Medicine, Science |
| More Details: |
Nuclear all-trans retinoic acid receptors (RARs) initiate early transcriptional events which engage pluripotent cells to differentiate into specific lineages. RAR-controlled transactivation depends mostly on agonist-induced structural transitions in RAR C-terminus (AF-2), thus bridging coactivators or corepressors to chromatin, hence controlling preinitiation complex assembly. However, the contribution of other domains of RAR to its overall transcriptional activity remains poorly defined. A proteomic characterization of nuclear proteins interacting with RAR regions distinct from the AF-2 revealed unsuspected functional properties of the RAR N-terminus. Indeed, mass spectrometry fingerprinting identified the Bromodomain-containing protein 4 (BRD4) and ALL1-fused gene from chromosome 9 (AF9/MLLT3), known to associate with and regulates the activity of Positive Transcription Elongation Factor b (P-TEFb), as novel RAR coactivators. In addition to promoter sequences, RAR binds to genomic, transcribed regions of retinoid-regulated genes, in association with RNA polymerase II and as a function of P-TEFb activity. Knockdown of either AF9 or BRD4 expression affected differentially the neural differentiation of stem cell-like P19 cells. Clusters of retinoid-regulated genes were selectively dependent on BRD4 and/or AF9 expression, which correlated with RAR association to transcribed regions. Thus RAR establishes physical and functional links with components of the elongation complex, enabling the rapid retinoid-induced induction of genes required for neuronal differentiation. Our data thereby extends the previously known RAR interactome from classical transcriptional modulators to components of the elongation machinery, and unravel a functional role of RAR in transcriptional elongation. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1932-6203 |
| Relation: |
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23762261/?tool=EBI; https://doaj.org/toc/1932-6203 |
| DOI: |
10.1371/journal.pone.0064880 |
| Access URL: |
https://doaj.org/article/65662d84c5e14954949695af67b93e71 |
| Accession Number: |
edsdoj.65662d84c5e14954949695af67b93e71 |
| Database: |
Directory of Open Access Journals |
