Epigenetic profiling reveals a developmental decrease in promoter accessibility of regeneration associated genes in CNS neurons

Society for Neuroscience Chicago 2015 Central Nervous System Regeneration Transplantation and Regeneration Support: The Bryon Riesch foundation SCIS/U2FP Unite 2 Fight Paralysis

Title: Epigenetic profiling reveals a developmental decrease in promoter accessibility of regeneration associated genes in CNS neurons

Authors: *I. VENKATESH, M. SIMPSON, B. CALLIF, M. BLACKMORE; Dept. of Biomed. Sci., Marquette Univ., Milwaukee, WI

Abstract: Embryonic neurons and peripheral neurons respond to axonal injury with activation of transcriptional programs conducive to regrowth. In contrast, mature CNS neurons fail to reactivate expression of crucial regeneration associated genes (RAGs) in response to injury, resulting in failed axon growth and permanent loss of function. Forced re-expression of key RAGs in mature CNS neurons is a promising strategy for therapeutic intervention. We and others have previously shown that ectopic expression of pro-regenerative factors such as KLF7 and Sox11 promotes axon regeneration in CNS neurons. Growth is incomplete however hinting that additional factors limit the cell intrinsic ability to promote growth. One reason could be restricted DNA accessibility due to a closed chromatin conformation in genomic loci corresponding to key RAGs in CNS neurons. We hypothesized that the developmental decline in regenerative ability is accompanied by a corresponding decrease in RAG promoter accessibility for pro-regenerative transcription factors. To test this, we profiled the epigenetic landscape surrounding promoters of select RAGs across development for changes in histone modifications indicative of DNA accessibility. We observed that RAGs including KLF7, Sox11, cJUN and GAP-43 switch from a relaxed chromatin environment to a restricted chromatin state as CNS neurons age. We are currently combining pro-regenerative TFs along with treatments that relax chromatin in assays of axon outgrowth. Overall, understanding changes in the chromatin landscape as CNS neurons mature, opens up the possibility of manipulating epigenetic modifications to promote axon outgrowth after injury.

Disclosures: I. Venkatesh: None. M. Simpson: None. B. Callif: None. M. Blackmore: None.

This entry was posted in Neuroscience Abstracts and tagged , . Bookmark the permalink.