Epigenomic signatures underpin the axonal regenerative ability of dorsal root ganglia sensory neurons.

Acetylation Algorithms Animals Axons / physiology CCCTC-Binding Factor / genetics Chromatin / metabolism Epigenomics Female Ganglia, Spinal / injuries Gene Expression Histones / metabolism Machine Learning Male Mice Mice, Transgenic Nerve Regeneration / physiology Sciatic Nerve / injuries Sensory Receptor Cells / physiology Sequence Analysis, RNA

Journal

Nature neuroscience
ISSN: 1546-1726
Titre abrégé: Nat Neurosci
Pays: United States
ID NLM: 9809671

Informations de publication

Date de publication:
11 2019
Historique:
received: 05 04 2018
accepted: 07 08 2019
pubmed: 9 10 2019
medline: 1 2 2020
entrez: 9 10 2019
Statut: ppublish

Résumé

Axonal injury results in regenerative success or failure, depending on whether the axon lies in the peripheral or the CNS, respectively. The present study addresses whether epigenetic signatures in dorsal root ganglia discriminate between regenerative and non-regenerative axonal injury. Chromatin immunoprecipitation for the histone 3 (H3) post-translational modifications H3K9ac, H3K27ac and H3K27me3; an assay for transposase-accessible chromatin; and RNA sequencing were performed in dorsal root ganglia after sciatic nerve or dorsal column axotomy. Distinct histone acetylation and chromatin accessibility signatures correlated with gene expression after peripheral, but not central, axonal injury. DNA-footprinting analyses revealed new transcriptional regulators associated with regenerative ability. Machine-learning algorithms inferred the direction of most of the gene expression changes. Neuronal conditional deletion of the chromatin remodeler CCCTC-binding factor impaired nerve regeneration, implicating chromatin organization in the regenerative competence. Altogether, the present study offers the first epigenomic map providing insight into the transcriptional response to injury and the differential regenerative ability of sensory neurons.

Identifiants

DOI: 10.1038/s41593-019-0490-4 PMID: 31591560
pubmed: 31591560
doi: 10.1038/s41593-019-0490-4
pii: 10.1038/s41593-019-0490-4
doi:

Substances chimiques

CCCTC-Binding Factor 0
Chromatin 0
Ctcf protein, mouse 0
Histones 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1913-1924

Subventions

Organisme : Medical Research Council
ID : MC_U120027516
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T003111/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom

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Auteurs

Ilaria Palmisano (I)

Division of Neuroscience, Department of Brain Sciences, Imperial College London, London, UK. i.palmisa@imperial.ac.uk.
ORCID: 0000-0002-7139-8090

Matt C Danzi (MC)

The Miami Project to Cure Paralysis, University of Miami, Miami, FL, USA.
Center for Computational Science, University of Miami, Miami, FL, USA.
ORCID: 0000-0003-1568-5965

Thomas H Hutson (TH)

Division of Neuroscience, Department of Brain Sciences, Imperial College London, London, UK.

Luming Zhou (L)

Division of Neuroscience, Department of Brain Sciences, Imperial College London, London, UK.

Eilidh McLachlan (E)

Division of Neuroscience, Department of Brain Sciences, Imperial College London, London, UK.

Elisabeth Serger (E)

Division of Neuroscience, Department of Brain Sciences, Imperial College London, London, UK.

Kirill Shkura (K)

Integrative Genomics and Medicine, Division of Neuroscience, Department of Brain Sciences, Imperial College London, London, UK.

Prashant K Srivastava (PK)

Integrative Genomics and Medicine, Division of Neuroscience, Department of Brain Sciences, Imperial College London, London, UK.
National Heart & Lung Institute, Imperial College London, London, UK.

Arnau Hervera (A)

Division of Neuroscience, Department of Brain Sciences, Imperial College London, London, UK.
Molecular and Cellular Neurobiotechnology, Institute for Bioengineering of Catalonia, Barcelona, Spain.

Nick O' Neill (NO)

The Miami Project to Cure Paralysis, University of Miami, Miami, FL, USA.

Tong Liu (T)

Department of Computer Science, University of Miami, Miami, FL, USA.

Hassen Dhrif (H)

Department of Computer Science, University of Miami, Miami, FL, USA.
ORCID: 0000-0002-3842-1762

Zheng Wang (Z)

Department of Computer Science, University of Miami, Miami, FL, USA.

Miroslav Kubat (M)

Department of Electrical & Computer Engineering, University of Miami, Miami, FL, USA.

Stefan Wuchty (S)

Center for Computational Science, University of Miami, Miami, FL, USA.
Department of Computer Science, University of Miami, Miami, FL, USA.
Department of Biology, University of Miami, Miami, FL, USA.
Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.

Matthias Merkenschlager (M)

MRC London Institute of Medical Sciences, Imperial College London, London, UK.

Liron Levi (L)

Faculty of Medicine, Bar Ilan University, Safed, Israel.

Evan Elliott (E)

Faculty of Medicine, Bar Ilan University, Safed, Israel.

John L Bixby (JL)

The Miami Project to Cure Paralysis, University of Miami, Miami, FL, USA.
Center for Computational Science, University of Miami, Miami, FL, USA.

Vance P Lemmon (VP)

The Miami Project to Cure Paralysis, University of Miami, Miami, FL, USA.
Center for Computational Science, University of Miami, Miami, FL, USA.

Simone Di Giovanni (S)

Division of Neuroscience, Department of Brain Sciences, Imperial College London, London, UK. s.di-giovanni@imperial.ac.uk.
ORCID: 0000-0003-3154-5399

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Classifications MeSH

Recherchemedicale.com › Métabolisme › Acylation › Acétylation › Epigenomic signatures underpin the axonal...
Recherchemedicale.com › Sciences de l'information › Méthodologies informatiques › Algorithmes › Epigenomic signatures underpin the axonal...
Recherchemedicale.com › Eucaryotes › Animaux › Epigenomic signatures underpin the axonal...
Recherchemedicale.com › Cellules › Neurones › Neurofibres › Axones › Epigenomic signatures underpin the axonal...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéines de répression › Facteur de liaison à la séquence CCCTC › Epigenomic signatures underpin the axonal...
Recherchemedicale.com › Phénomènes génétiques › Structures génétiques › Structures de chromosome › Chromatine › Epigenomic signatures underpin the axonal...
Recherchemedicale.com › Disciplines des sciences naturelles › Disciplines des sciences biologiques › Biologie › Génétique › Génomique › Épigénomique › Epigenomic signatures underpin the axonal...
Recherchemedicale.com › Système nerveux › Système nerveux périphérique › Nerfs périphériques › Nerfs spinaux › Racines des nerfs spinaux › Ganglions sensitifs des nerfs spinaux › Epigenomic signatures underpin the axonal...
Recherchemedicale.com › Phénomènes génétiques › Expression des gènes › Epigenomic signatures underpin the axonal...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Histone › Epigenomic signatures underpin the axonal...
Recherchemedicale.com › Sciences de l'information › Méthodologies informatiques › Algorithmes › Intelligence artificielle › Apprentissage machine › Epigenomic signatures underpin the axonal...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Epigenomic signatures underpin the axonal...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Epigenomic signatures underpin the axonal...
Recherchemedicale.com › Phénomènes biologiques › Régénération › Régénération nerveuse › Epigenomic signatures underpin the axonal...
Recherchemedicale.com › Système nerveux › Système nerveux périphérique › Nerfs périphériques › Nerfs spinaux › Plexus lombosacral › Nerf ischiatique › Epigenomic signatures underpin the axonal...
Recherchemedicale.com › Cellules › Neurones › Neurones afférents › Cellules réceptrices sensorielles › Epigenomic signatures underpin the axonal...
Recherchemedicale.com › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ARN › Epigenomic signatures underpin the axonal...