ArticlePLoS biology2022
ERK1/2 signalling dynamics promote neural differentiation by regulating chromatin accessibility and the polycomb repressive complex.
Article in PLoS biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
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- A New Insight in Cellular and Molecular Signaling Regulation for Neural Differentiation Program.Molecular neurobiology · 2025Review
- A dual enhancer-attenuator element ensures transient Cdx2 expression during mouse posterior body formation.Developmental cell · 2025Article
- RNMT-dependent RNA cap methylation in health and disease.The Biochemical journal · 2025Review
- Genome-wide CRISPR screen identifies Menin and SUZ12 as regulators of human developmental timing.Nature cell biology · 2025Article
- Onco-Ontogeny of Squamous Cell Cancer of the First Pharyngeal Arch Derivatives.International journal of molecular sciences · 2024Review
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- Notch signalling influences cell fate decisions and HOX gene induction in axial progenitors.Development (Cambridge, England) · 2024Article
- Acquisition of neural fate by combination of BMP blockade and chromatin modification.iScience · 2023Article
- Dynamics of an incoherent feedforward loop drive ERK-dependent pattern formation in the early Drosophila embryo.Development (Cambridge, England) · 2023Article
- Dynamics of an incoherent feedforward loop drive ERK-dependent pattern formation in the earlybioRxiv : the preprint server for biology · 2023Article
- Certain ortho-hydroxylated brominated ethers are promiscuous kinase inhibitors that impair neuronal signaling and neurodevelopmental processes.The Journal of biological chemistry · 2020Article
- Enhancer activation by FGF signalling during otic induction.Developmental biology · 2020Article
- Differentiation of Mesenchymal Stem Cells to Neuroglia: in the Context of Cell Signalling.Stem cell reviews and reports · 2019Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Fibroblast growth factor (FGF) is a neural inducer in many vertebrate embryos, but how it regulates chromatin organization to coordinate the activation of neural genes is unclear. Moreover, for differentiation to progress, FGF signalling must decline. Why these signalling dynamics are required has not been determined. Here, we show that dephosphorylation of the FGF effector kinase ERK1/2 rapidly increases chromatin accessibility at neural genes in mouse embryos, and, using ATAC-seq in human embryonic stem cell derived spinal cord precursors, we demonstrate that this occurs genome-wide across neural genes. Importantly, ERK1/2 inhibition induces precocious neural gene transcription, and this involves dissociation of the polycomb repressive complex from key gene loci. This takes place independently of subsequent loss of the repressive histone mark H3K27me3 and transcriptional onset. Transient ERK1/2 inhibition is sufficient for the dissociation of the repressive complex, and this is not reversed on resumption of ERK1/2 signalling. Moreover, genomic footprinting of sites identified by ATAC-seq together with ChIP-seq for polycomb protein Ring1B revealed that ERK1/2 inhibition promotes the occupancy of neural transcription factors (TFs) at non-polycomb as well as polycomb associated sites. Together, these findings indicate that ERK1/2 signalling decline promotes global changes in chromatin accessibility and TF binding at neural genes by directing polycomb and other regulators and appears to serve as a gating mechanism that provides directionality to the process of differentiation.
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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.