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

Ilaria Palmisano, Matt C. Danzi, Thomas H. Hutson, Luming Zhou, Eilidh McLachlan, Elisabeth Serger, Kirill Shkura, Prashant K. Srivastava, Arnau Hervera, Nick O’ Neill, Tong Liu, Hassen Dhrif, Zheng Wang, Miroslav Kubat, Stefan Wuchty, Matthias Merkenschlager, Liron Levi, Evan Elliott, John L. Bixby, Vance P. LemmonSimone Di Giovanni

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1913-1924
Number of pages12
JournalNature Neuroscience
Volume22
Issue number11
DOIs
StatePublished - Nov 1 2019

ASJC Scopus subject areas

  • Neuroscience(all)

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