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A novel nuclear FGF Receptor‐1 partnership with retinoid and Nur receptors during developmental gene programming of embryonic stem cells
Author(s) -
Lee YuWei,
Terranova Christopher,
Birkaya Barbara,
Narla Sridhar,
Kehoe Daniel,
Parikh Abhirath,
Dong Shuo,
Ratzka Andreas,
Brinkmann Hella,
Aletta John M.,
Tzanakakis Emmanuel S.,
Stachowiak Ewa K.,
Claus Peter,
Stachowiak Michal K.
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24170
Subject(s) - fibroblast growth factor receptor 1 , biology , retinoid x receptor , nuclear receptor , microbiology and biotechnology , transcription factor , fibroblast growth factor , retinoic acid , receptor tyrosine kinase , fgf8 , cancer research , receptor , signal transduction , genetics , gene
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. J. Cell. Biochem. 113: 2920–2936, 2012. © 2012 Wiley Periodicals, Inc.