Can Chromatin Accessibility be Exploited for Axon Regeneration?

Figure 1:. Diagram summarizing the effects on chromatin accessibility of three axon regeneration-promoting interventions. A) PTEN in a complex with nucleosomes. Deletion of PTEN prevents the binding of Histone H1 to DNA and thereby promotes chromatin accessibility. B) Enhancement of neuronal activity induces expression of AP-1 factors, mediating chromatin opening and activating transcription. C) Overexpression of TET enzymes catalyzes conversion of 5-methylcytosine (5mc) to 5-hydroxymethylcytosine (5hmc), thereby promoting chromatin opening.

Can Chromatin Accessibility be Exploited for Axon Regeneration?

Several studies have demonstrated that the intrinsic ability of neurons to regenerate their axons can be stimulated by maneuvers that favor the open state of chromatin, such as inhibiting histone deacetylase activity or increasing histone acetyltransferase activity. Taken together, these experiments suggest . . .that axon regenerative ability can be increased by promoting chromatin accessibility. In this article, we assess the direct evidence in the literature for this hypothesis and re-examine other axon regeneration-promoting manipulations to see if they provide additional support. We find that several interventions known to enhance intrinsic axonal growth capability also increase chromatin accessibility. Although the support for this correlation is strong in the literature, we conclude with a word of caution about therapeutics attempting to exploit this relationship.

 

 2018 Apr 17. doi: 10.1002/dneu.22598. [Epub ahead of print] Danzi MC, O’Neill N, Bixby JL, Lemmon VP. PMID: 29664188 DOI: 10.1002/dneu.22598