Fibroblast growth factor receptor 2 homodimerization rapidly reduces transcription of the pluripotency gene Nanog without dissociation of activating transcription factors.

ABSTRACT: Nanog or Gata6-positive cells co-exist and are convertible within the inner cell mass of murine blastocysts and embryonic stem (ES) cells. Previous studies demonstrate fibroblast growth factor receptor 2 (FGFR2) triggers Nanog gene down-regulation and differentiation to primitive endoderm (PE); however, the underlying mechanisms responsible for reversible and fluctuating cell fate are poorly understood. Using an inducible FGFR2 dimerization system in ES cells, we demonstrate that FGFR2 activation rapidly down-regulated Nanog gene transcription through activation of the Mek pathway and subsequently differentiated ES cells into PE cells. FGFR2 rather selectively repressed the Nanog gene with minimal effect on other pluripotency genes, including Oct4 and Sox2. We determined the Nanog promoter

SUBMITTER: Santostefano KE 

PROVIDER: S-EPMC3436299 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature