ArticleThe EMBO journal2019
PP4-dependent HDAC3 dephosphorylation discriminates between axonal regeneration and regenerative failure.
Article in The EMBO journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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The trial behind it
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Who cites it
35 citing papers in PubMed, 52 citations in OpenAlex.
- Exercise training promotes nerve cell repair and regeneration after spinal cord injury.Neural regeneration research · 2026Article
- CITED2 is a druggable epigenetic switch coupling neuronal maturation to regenerative decline.EMBO molecular medicine · 2026Article
- Suppressing DBNDD2 promotes neuron growth and axon regeneration in adult mammals.Frontiers of medicine · 2025Article
- HDAC3 Serine 424 Phospho-mimic and Phospho-null Mutants Bidirectionally Modulate Long-Term Memory Formation and Synaptic Plasticity in the Adult and Aging Mouse Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Histone Acetylation in Central and Peripheral Nervous System Injuries and Regeneration: Epigenetic Dynamics and Therapeutic Perspectives.International journal of molecular sciences · 2025Review
- The Role of Methylation Modification in Neural Injury and Repair.International journal of molecular sciences · 2025Review
- Three-dimensional chromatin mapping of sensory neurons reveals that promoter-enhancer looping is required for axonal regeneration.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Three-dimensional chromatin mapping of sensory neurons reveals that cohesin-dependent genomic domains are required for axonal regeneration.bioRxiv : the preprint server for biology · 2024Article
- Unleashing Axonal Regeneration Capacities: Neuronal and Non-neuronal Changes After Injuries to Dorsal Root Ganglion Neuron Central and Peripheral Axonal Branches.Molecular neurobiology · 2024Review
- Pharmacological HDAC3 inhibition alters memory updating in young and old male mice.Frontiers in molecular neuroscience · 2024Article
- Regulation of axonal regeneration after mammalian spinal cord injury.Nature reviews. Molecular cell biology · 2023Review
- Selective Targeting of Class I HDAC Reduces Microglial Inflammation in the Entorhinal Cortex of Young APP/PS1 Mice.International journal of molecular sciences · 2023Article
- Subacute and Chronic Spinal Cord Injury: A Scoping Review of Epigenetics and Secondary Health Conditions.Epigenetics insights · 2023Article
- HDAC2 in Primary Sensory Neurons Constitutively Restrains Chronic Pain by Repressing α2δ-1 Expression and Associated NMDA Receptor Activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- CBP/p300 activation promotes axon growth, sprouting, and synaptic plasticity in chronic experimental spinal cord injury with severe disability.PLoS biology · 2022Article
- Purification of mouse axoplasmic proteins from dorsal root ganglia nerves for proteomics analysis.STAR protocols · 2022Article
- Emerging Role of HDACs in Regeneration and Ageing in the Peripheral Nervous System: Repair Schwann Cells as Pivotal Targets.International journal of molecular sciences · 2022Review
- Analysis of neuronal injury transcriptional response identifies CTCF and YY1 as co-operating factors regulating axon regeneration.Frontiers in molecular neuroscience · 2022Article
- Phenotypic Screening Following Transcriptomic Deconvolution to Identify Transcription Factors Mediating Axon Growth Induced by a Kinase Inhibitor.SLAS discovery : advancing life sciences R & D · 2021Article
- Genome-wide chromatin accessibility analyses provide a map for enhancing optic nerve regeneration.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 4 countries.
Funding
Abstract
The molecular mechanisms discriminating between regenerative failure and success remain elusive. While a regeneration-competent peripheral nerve injury mounts a regenerative gene expression response in bipolar dorsal root ganglia (DRG) sensory neurons, a regeneration-incompetent central spinal cord injury does not. This dichotomic response offers a unique opportunity to investigate the fundamental biological mechanisms underpinning regenerative ability. Following a pharmacological screen with small-molecule inhibitors targeting key epigenetic enzymes in DRG neurons, we identified HDAC3 signalling as a novel candidate brake to axonal regenerative growth. In vivo, we determined that only a regenerative peripheral but not a central spinal injury induces an increase in calcium, which activates protein phosphatase 4 that in turn dephosphorylates HDAC3, thus impairing its activity and enhancing histone acetylation. Bioinformatics analysis of ex vivo H3K9ac ChIPseq and RNAseq from DRG followed by promoter acetylation and protein expression studies implicated HDAC3 in the regulation of multiple regenerative pathways. Finally, genetic or pharmacological HDAC3 inhibition overcame regenerative failure of sensory axons following spinal cord injury. Together, these data indicate that PP4-dependent HDAC3 dephosphorylation discriminates between axonal regeneration and regenerative failure.
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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.