Epigenomic signatures underpin the axonal regenerative ability of dorsal root ganglia sensory neurons
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2019-10-07
Date Acceptance
2019-08-07
Citation
Nature Neuroscience, 2019, 22 (11), pp.1913-1924
ISSN
1097-6256
Publisher
Springer Science and Business Media LLC
Start Page
1913
End Page
1924
Journal / Book Title
Nature Neuroscience
Volume
22
Issue
11
Copyright Statement
© The Author(s), under exclusive licence to Springer Nature America, Inc. 2019. The final publication is available at Springer via https://doi.org/10.1038/s41593-019-0490-4
Sponsor
Wings for Life Spinal Cord Research Foundation
Rosetrees Trust
Wellcome Trust
Medical Research Council (MRC)
Identifier
https://www.nature.com/articles/s41593-019-0490-4
Grant Number
WFL-GB-021/13
A1949/ M434-F1
099276/Z/12/Z
PO4050659629
Subjects
1109 Neurosciences
1702 Cognitive Sciences
1701 Psychology
Neurology & Neurosurgery
Publication Status
Published
Date Publish Online
2019-10-07