ArticleThe Journal of biological chemistry2012
Fibroblast growth factor receptor 2 homodimerization rapidly reduces transcription of the pluripotency gene Nanog without dissociation of activating transcription factors.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- A NANOG-pERK reciprocal regulatory circuit regulates Nanog autoregulation and ERK signaling dynamics.EMBO reports · 2022Article
- A Sprouty4 reporter to monitor FGF/ERK signaling activity in ESCs and mice.Developmental biology · 2018Article
- ICM conversion to epiblast by FGF/ERK inhibition is limited in time and requires transcription and protein degradation.Scientific reports · 2017Article
- Four simple rules that are sufficient to generate the mammalian blastocyst.PLoS biology · 2017Article
- Distinct Requirements for FGFR1 and FGFR2 in Primitive Endoderm Development and Exit from Pluripotency.Developmental cell · 2017Article
- The deubiquitinase USP21 maintains the stemness of mouse embryonic stem cells via stabilization of Nanog.Nature communications · 2016Article
- A reciprocal regulatory circuit between CD44 and FGFR2 via c-myc controls gastric cancer cell growth.Oncotarget · 2016Article
- Leukemia inhibitory factor (LIF) withdrawal activates mTOR signaling pathway in mouse embryonic stem cells through the MEK/ERK/TSC2 pathway.Cell death & disease · 2016Article
- Primitive endoderm differentiation: from specification to epithelium formation.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2014Review
- GATA6 levels modulate primitive endoderm cell fate choice and timing in the mouse blastocyst.Developmental cell · 2014Article
- Brf1 posttranscriptionally regulates pluripotency and differentiation responses downstream of Erk MAP kinase.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Concise review: pursuing self-renewal and pluripotency with the stem cell factor Nanog.Stem cells (Dayton, Ohio) · 2013Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
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 region containing minimum Oct4/Sox2 binding sites was sufficient for this transcriptional down-regulation by FGFR2, when the reporter transgenes were integrated with insulators. Of interest, FGFR2-mediated Nanog transcriptional reduction occurred without dissociation of RNA polymerase II, p300, Oct4, Sox2, and Tet1 from the Nanog proximal promoter region and with no increase in repressive histone methylation marks or DNA methylation, implying the gene repression is in the early and transient phase. Furthermore, addition of a specific FGFR inhibitor readily reversed this Nanog repression status. These findings illustrate well how FGFR2 induces rapid but reversible Nanog repression within ES cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.