A novel nuclear FGF Receptor-1 partnership with retinoid and Nur receptors during developmental gene programming of embryonic stem cells
| Autor: | Shuo Dong, John M. Aletta, Abhirath Parikh, Yu Wei Lee, Hella Brinkmann, Peter Claus, Barbara Birkaya, Michal K. Stachowiak, Daniel Kehoe, Andreas Ratzka, Emmanuel S. Tzanakakis, Sridhar T. Narla, Christopher Terranova, Ewa K. Stachowiak |
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| Rok vydání: | 2012 |
| Předmět: |
Chromatin Immunoprecipitation
Nerve growth factor IB Receptors Retinoic Acid Blotting Western Retinoic acid Retinoid X receptor Biology Fibroblast growth factor Biochemistry chemistry.chemical_compound Humans Immunoprecipitation Receptor Fibroblast Growth Factor Type 1 Molecular Biology Cells Cultured Embryonic Stem Cells Regulation of gene expression Cell Biology Orphan Nuclear Receptors Embryonic stem cell Molecular biology Immunohistochemistry stomatognathic diseases chemistry embryonic structures Chromatin immunoprecipitation Tyrosine kinase Fluorescence Recovery After Photobleaching |
| Zdroj: | Journal of cellular biochemistry. 113(9) |
| ISSN: | 1097-4644 |
| Popis: | FGF Receptor-1 (FGFR1), a membrane-targeted protein, is also involved in independent direct nuclear signaling. We show that nuclear accumulation of FGFR1 is a common response to retinoic acid (RA) in pluripotent embryonic stem cells (ESC) and neural progenitors and is both necessary and sufficient for neuronal-like differentiation and accompanying neuritic outgrowth. Dominant negative nuclear FGFR1, which lacks the tyrosine kinase domain, prevents RA-induced differentiation while full-length nuclear FGFR1 elicits differentiation in the absence of RA. Immunoprecipitation and GST assays demonstrate that FGFR1 interacts with RXR, RAR and their Nur77 and Nurr1 partners. Conditions that promote these interactions decrease the mobility of nuclear FGFR1 and RXR in live cells. RXR and FGFR1 co-associate with 5'-Fluorouridine-labeled transcription sites and with RA Responsive Elements (RARE). RA activation of neuronal (tyrosine hydroxylase) and neurogenic (fgf-2 and fgfr1) genes is accompanied by increased FGFR1, Nur, and histone H3.3 binding to their regulatory sequences. Reporter-gene assays show synergistic activations of RARE, NBRE, and NurRE by FGFR1, RAR/RXR, and Nurs. As shown for mESC differentiation, FGFR1 mediates gene activation by RA and augments transcription in the absence of RA. Cooperation of FGFR1 with RXR/RAR and Nurs at targeted genomic sequences offers a new mechanism in developmental gene regulation. |
| Databáze: | OpenAIRE |
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