Document Type

Article

Language

eng

Format of Original

8 p.

Publication Date

12-2016

Publisher

Elsevier

Source Publication

Neuroepigenetics

Source ISSN

2214-7845

Original Item ID

DOI: 10.1016/j.nepig.2016.10.002; PMID: 27990351

Abstract

Axon regeneration in adult central nervous system (CNS) is limited in part by a developmental decline in the ability of injured neurons to re-express needed regeneration associated genes (RAGs). Adult CNS neurons may lack appropriate pro-regenerative transcription factors, or may display chromatin structure that restricts transcriptional access to RAGs. Here we performed epigenetic profiling around the promoter regions of key RAGs, and found progressive restriction across a time course of cortical maturation. These data identify a potential intrinsic constraint to axon growth in adult CNS neurons. Neurite outgrowth from cultured postnatal cortical neurons, however, proved insensitive to treatments that improve axon growth in other cell types, including combinatorial overexpression of AP1 factors, overexpression of histone acetyltransferases, and pharmacological inhibitors of histone deacetylases. This insensitivity could be due to intermediate chromatin closure at the time of culture, and highlights important differences in cell culture models used to test potential pro-regenerative interventions.

Comments

Published version. Neuroepigenetics, Vol. 8 (December 2016): 19-26. DOI. © 2016 The Authors. Used with permission.

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