Table 1.
Histone modifications associated with axon growth potential.
| Histone codes | Epigenetic factors | Neuron type | Experimental models | Molecular targets | Ref. |
|---|---|---|---|---|---|
| H3ac | HDAC5 | Adult DRG neurons | Peripheral nerve regeneration Nuclear exit elicited by retro-propagation of Ca2+ wave upon axotomy |
Jun, Fos, Klf | (Cho et al., 2013) |
| H4ac | HDAC1 p300 |
Adult DRG neurons | Sensory axon regeneration in SCI model Smad1 recruits p300 and displaces HDAC1 at promoters of target genes |
Sprr1a, Npy, Galanin, Vip | (Finelli et al., 2013b) |
| H3K9ac (gene activation) H3K9me2 (gene silencing) |
• PCAF • (an H3K9ac-specific HAT) • No changes in H3K18ac, H3K4me2 or H3K27me3 that correlated with RAGs changes |
Adult DRG neurons | • PCAF activated by pERK-mediated retrograde signaling after axotomy • AAV-PCAF promotes neurite outgrowth on laminin and myelin and ascending sensory axon regeneration after dorsal column SCI • PCAF-/- DRG neurons show abolished axon growth induced by periphery axotomy in culture and in SCI model |
Gap43, Galanin, Bdnf, but not at Sprr1a, Atf3, Hsp27: proximal promoters exhibit enriched H3K9ac and depleted H3K9me2 after peripheral axotomy | (Puttagunta et al., 2014) |
| H3K9me3 | - | Adult DRG neurons | Sciatic nerve injury model UHRF1 interacts with H3K9me3 and DNMTs at the promoter region to repress gene expression by promoter methylation |
PTEN, CDKN1A, REST (H3K9me3 enriched at CpG promoter region after peripheral axotomy) | (Oh et al., 2018) |
| H3K9ac H3K14ac |
HDAC (Class I and II) inhibition by TSA, PB increases H3K9ac, H3K14ac CBP/p300 or PCAF knockdown reduces H3K9ac, H3K14ac |
P7 Cerebellar granule cells Cortical neurons |
• H3K9ac and H3K14ac decline during development • TSA → Increased neurite outgrowth on both permissive and non-permissive substrates (myelin or CSPG) in vitro |
• Gap43 and Coronin1b (TSA→H3K9ac/ • H3K14ac at promoters) • CBP/p300 and PCAF (TSA→ H3ac at HAT promoters) • p53 (acetylation by TSA) |
(Gaub et al., 2010) |
| H3K18ac | p300 | RGC (retinal ganglion cell) | • H3K18ac and p300 levels decline during RGC maturation • Adenoviral overexpression of p300→ axon regeneration in optic N crush model • TSA→ no RGC regeneration, but enhances RGC survival |
• p300 binds to promoters of Gap43, Coronin1b and Sprr1a • p300 increases H3K18ac • p300 increases p53 ac and C/EBP ac |
(Gaub et al., 2011) |
| H3K4me3 (euchromatin marker) H3K27me3 (hetero-chromatin marker) |
- | Embryonic vs. postnatal cortical neurons | Cortices from E15, P3, P7, P14, P21 and adult In postnatal cortical neurons, overexpression of KAT2A and KAT2B (PCAF) did not affect neurite outgrowth, nor did HDAC inhibitor TSA and Scriptaid |
• H3K4me3 enriched at promoters of Sprr1a, Integrin α7, Galanin, and Gap43 in E15 vs. adult cortex, but not at Hsp27 and Cap23 • H3K27me3 enriched in adult cortex vs. embryonic in these RAGs |
(Venkatesh et al., 2016) |