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.
|Number of pages||12|
|State||Published - 1 Nov 2019|
Bibliographical noteFunding Information:
We would like to acknowledge the start-up funds: Division of Brain Sciences, Imperial College London (S.D.G.), Wings for Life grant no. WFL-UK-07/16 (S.D.G.), Rosetrees Trust grant no. A1438 (S.D.G.), the Leverhulme Trust grant no. RPG-2015-092 (S.D.G.), ISRT (S.D.G.), the Medical Research Council grant no. R/R005311/1 (S.D.G.) and WT grant no. 099276/Z/12/Z (M.M.). The research was supported by the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre (S.D.G.). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. We thank C. Sibley, Imperial College London, for useful discussion and suggestions.
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.