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.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Palmisano I,Danzi MC,Hutson TH,Zhou L,McLachlan E,Serger E,Shkura K,Srivastava PK,Hervera A,Neill NO,Liu T,Dhrif H,Wang Z,Kubat M,Wuchty S,Merkenschlager M,Levi L,Elliott E,Bixby JL,Lemmon VP,Di Giovanni Sdoi
10.1038/s41593-019-0490-4subject
Has Abstractpub_date
2019-11-01 00:00:00pages
1913-1924issue
11eissn
1097-6256issn
1546-1726pii
10.1038/s41593-019-0490-4journal_volume
22pub_type
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