Epigenetic Regulation of Sensory Axon Regeneration After Spinal Cord Injury

Overview

Journal J Neurosci

Specialty Neurology

Date 2013 Dec 17

PMID 24336730

Citations 86

Authors

Mattea J Finelli

Jamie K Wong

Hongyan Zou

Affiliations

Soon will be listed here.

Abstract

Axon regeneration is hindered by a decline of intrinsic axon growth capability in mature neurons. Reversing this decline is associated with the induction of a large repertoire of regeneration-associated genes (RAGs), but the underlying regulatory mechanisms of the transcriptional changes are largely unknown. Here, we establish a correlation between diminished axon growth potential and histone 4 (H4) hypoacetylation. When neurons are triggered into a growth state, as in the conditioning lesion paradigm, H4 acetylation is restored, and RAG transcription is initiated. We have identified a set of target genes of Smad1, a proregenerative transcription factor, in conditioned DRG neurons. We also show that, during the epigenetic reprogramming process, histone-modifying enzymes work together with Smad1 to facilitate transcriptional regulation of RAGs. Importantly, targeted pharmacological modulation of the activity of histone-modifying enzymes, such as histone deacetylases, leads to induction of multiple RAGs and promotion of sensory axon regeneration in a mouse model of spinal cord injury. Our findings suggest epigenetic modulation as a potential therapeutic strategy to enhance axon regeneration.

Citing Articles

Axonal Regeneration after Spinal Cord Injury: Molecular Mechanisms, Regulatory Pathways, and Novel Strategies.

Elmalky M, Alvarez-Bolado G, Younsi A, Skutella T Biology (Basel). 2024; 13(9).

PMID: 39336130 PMC: 11428726. DOI: 10.3390/biology13090703.

Three-dimensional chromatin mapping of sensory neurons reveals that promoter-enhancer looping is required for axonal regeneration.

Palmisano I, Liu T, Gao W, Zhou L, Merkenschlager M, Mueller F Proc Natl Acad Sci U S A. 2024; 121(38):e2402518121.

PMID: 39254997 PMC: 11420198. DOI: 10.1073/pnas.2402518121.

Roles of SMAD and SMAD-Associated Signaling Pathways in Nerve Regeneration Following Peripheral Nerve Injury: A Narrative Literature Review.

Lee J, Yon D, Choi Y, Lee J, Yeo J, Kim S Curr Issues Mol Biol. 2024; 46(7):7769-7781.

PMID: 39057101 PMC: 11276098. DOI: 10.3390/cimb46070460.

Three-dimensional chromatin mapping of sensory neurons reveals that cohesin-dependent genomic domains are required for axonal regeneration.

Palmisano I, Liu T, Gao W, Zhou L, Merkenschlager M, Muller F bioRxiv. 2024; .

PMID: 38895406 PMC: 11185766. DOI: 10.1101/2024.06.09.597974.

The Protein Acetylation after Traumatic Spinal Cord Injury: Mechanisms and Therapeutic Opportunities.

Li H, Zhang H Int J Med Sci. 2024; 21(4):725-731.

PMID: 38464830 PMC: 10920853. DOI: 10.7150/ijms.92222.

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