Table 2.
Epigenetic regulation of RAG expression.
| RAG | Epigenetic modification | Localization | Neuron type | Epigenetic modifier | Gene regulation | Reference |
|---|---|---|---|---|---|---|
| Atf3 | H4ac | Promoter | Adult DRG SNL 6 hr |
HDACi (MS275) no effect |
Gene upregulation correlated with H4ac enrichment at promoter 6 hr after SNL No H4ac enrichment or gene induction with HDAC1 inhibitor MS275 In N2A cells, pSmad1 promoter binding recruits p300 |
(Finelli et al., 2013b) |
| DNA demethylation | Distal Enhancers, but not promoter show DNA demethylation after SNL | Adult DRG neurons SNL day 1 |
Tet3 TDG |
Tet3 binds to Distal Enhancer Tet3 KD or TDG KD attenuates Atf3 induction in conditioned DRG DNA demethylation at DE1 of Atf3 after SNL requires Tet3 |
(Weng et al., 2017) | |
| 5hmC | Gene body | Adult DRG SNL day 1 |
Tet3 | Gene induction correlates with 5hmC gain | (Loh et al., 2017) | |
| m6A tagging | mRNA | Adult DRG SNL day 1 |
Mettl14 Ythdf1 |
Increase in both m6A-tagged and total Atf3 mRNA levels after SNL, Gained new m6A sites upon SNL Loss of m6A tagging of Aft3 mRNA reduces ATF3 protein translation |
(Weng et al., 2018) | |
| Bdnf | H3K9ac gain H3K9me2 loss | Promoter | Adult DRG SNL day 1 |
PCAF | Gene induction PCAF promoter occupancy increases upon SNL |
(Puttagunta et al., 2014) |
| 5hmC | Gene body (last exon) | Adult DRG SNL day 1 |
Tet3 | Gene induction correlates with 5hmC gain | (Loh et al., 2017) | |
| Myc | DNA demethylation | Distal enhancer sites show DNA demethylation after SNL | Adult DRG neurons SNL day 1 |
Tet3 TDG |
Tet3 KD or TDG KD attenuates Myc induction in conditioned DRG | (Weng et al., 2017) |
| Coronin 1b | H3ac | – | Cerebellar granule cells | HDACi (TSA) | TSA induces Coronin1b expression | (Gaub et al., 2010) |
| H3ac | Promoter | RGC Optic Nerve crush |
p300 | Upregulated with AV-p300 p300 promoter occupancy |
(Gaub et al., 2011) | |
| Gadd45a | DNA methylation | Promoter | Rat SCI with SNL | Dnmt3a Dnmt3b |
Upregulation Bilateral dorsal column transection |
(Iskandar et al., 2010) |
| m6A tagging | mRNA | Adult DRG SNL day 1 |
– | Increase in both m6A-tagged and total mRNA levels after SNL | (Weng et al., 2018) | |
| Galanin | H4ac | Promoter | Adult DRG SNL |
HDACi (MS275) | Gene upregulation correlated with H4ac enrichment at promoter 6 hr after SNL HDAC1 inhibitor leads to H4ac enrichment and gene induction In N2A cells, pSmad1 promoter binding displaces HDAC1 binding |
(Finelli et al., 2013b) |
| H3K9ac gain H3K9me2 loss | Promoter | Adult DRG SNL day 1 |
PCAF | Gene induction PCAF promoter occupancy increases upon SNL |
(Puttagunta et al., 2014) | |
| H3K4me3 | Promoter | Developing cortex | – | Enriched in E15 cortex and gradual decline during maturation | (Venkatesh et al., 2016) | |
| H3K27me3 | Promoter | Developing cortex | – | Low in E15 cortex, gradual increase during maturation | (Venkatesh et al., 2016) | |
| Gap43 | H3ac | – | Cerebellar granule cells | HDACi (TSA) | TSA induces Gap43 expression | (Gaub et al., 2010) |
| H3ac | Promoter | RGC Optic nerve crush |
p300 | Upregulation with AV-p300 p300 promoter occupancy |
(Gaub et al., 2011) | |
| H3K9ac gain H3K9me2 loss | Promoter | Adult DRG SNL day 1 |
PCAF | Gene induction PCAF promoter occupancy increase upon SNL |
(Puttagunta et al., 2014) | |
| H4ac | Promoter | Adult DRG | HDACi (MS275) no effect |
No H4ac enrichment at promoter 6 hr after SNL No H4ac enrichment or gene induction with HDAC1 inhibitor |
(Finelli et al., 2013b) | |
| H3K4me3 | Promoter | Developing cortex | – | Enriched in E15 cortices, gradual decline during maturation | (Venkatesh et al., 2016) | |
| H3K27me3 | Promoter | Developing cortex | – | Low in E15 cortices, gradual increase during maturation | (Venkatesh et al., 2016) | |
| No change in DNA demethylation | Distal enhancer | Adult DRG SNL |
TET3/TDG not involved | No change in DNA methylation status by bisulfite sequencing | (Weng et al., 2017) | |
| Integrin α7 | H3K4me3 | Promoter | Developing cortex | – | Enriched in E15 cortex, gradual decline during maturation | (Venkatesh et al., 2016) |
| H3K27me3 | Promoter | Developing cortex | – | Low in E15 cortex, gradual increase during maturation | (Venkatesh et al., 2016) | |
| Jun | m6A tagging | mRNA | Adult DRG SNL day 1 |
– | Increase in both m6A-tagged and total mRNA levels of Jun after SNL | (Weng et al., 2018) |
| Npy | H4ac | Promoter | Adult DRG SNL |
HDACi (MS275) | Gene upregulation correlated with H4ac enrichment at promoter after SNL HDAC1 inhibitor MS275 results in H4ac enrichment and gene induction In N2A cells, pSmad1 promoter binding displaces HDAC1 |
(Finelli et al., 2013b) |
| PTEN | DNA methylation H3K9me3 |
CpG promoter region | Adult DRG SNL |
DNMTs UHRF1 |
H3K9me3 enriched at the CpG promoter region of PTEN after SNL, UHRF1 interacts with DNMTs to represses PTEN via promoter methylation | (Oh et al., 2018) |
| REST | microRNA DNA methylation H3K9me3 |
3’UTR CpG promoter region |
Adult DRG SNL |
miR-9 DNMTs UHRF1 |
Upon SNL, transient increase of REST via downregulation of miR-9, later, reduced REST transcription via UHRF1-mediated promoter methylation | (Oh et al., 2018) |
| SIRT1 | microRNA | microRNA | Adult DRG neurons | miR-138 | SIRT1 induced after SNL, required for peripheral nerve regeneration, Downregulate GSK3β, Smad1 acts downstream of miR-26a-GSK3β pathway PTEN not affected |
(Jiang et al., 2015) |
| – | – | Embryonic cortical neurons | – | Promote neurite outgrowth and cell survival through mTOR signaling | (Guo et al., 2011b) | |
| Smad1 | H4ac | Promoter | Adult DRG SNL |
HDACi (MS275) no effect |
Gene upregulation correlated with H4ac enrichment at promoter 6 hr after SNL No H4ac enrichment or gene induction with HDAC1 inhibitor |
(Finelli et al., 2013b) |
| 5hmC loss | Introns | Adult DRG SNL day 1 |
Tet3 | Two introns both showing 5hmC loss after SNL | (Loh et al., 2017) | |
| DNA demethylation | – | Adult DRG SNL day 1 |
Tet3 TDG |
Tet3 KD or TDG KD attenuates Smad1 induction in conditioned DRG | (Weng et al., 2017) | |
| Sox11 | m6A tagging | mRNA | Adult DRG SNL day 1 |
– | Increase in both m6A-tagged and total mRNA levels of Sox11 after SNL | (Weng et al., 2018) |
| Sprr1a | H4ac | Promoter | Adult DRG SNL day 1 |
HDACi (MS275) |
Gene upregulation correlated with H4ac enrichment at promoter 6 hr after SNL HDAC1 inhibitor leads to H4ac enrichment and gene induction In N2A cells, pSmad1 promoter binding displaces HDAC1 and recruits p300 |
(Finelli et al., 2013b) |
| H3K9ac loss | Promoter | Adult DRG SNL |
– | Gene induction, but H3K9ac loss | (Puttagunta et al., 2014) | |
| H3ac | Promoter | RGC Optic nerve crush |
p300 | Upregulated with AV-p300 p300 promoter occupancy |
(Gaub et al., 2011) | |
| H3K4me3 | Promoter | Developing cortex | – | Enriched in E15 cortex, gradual decline during maturation | (Venkatesh et al., 2016) | |
| H3K27me3 | Promoter | Developing cortex | – | Low in E15 cortex, gradual increase during maturation | (Venkatesh et al., 2016) | |
| STAT3 | DNA demethylation | – | Adult DRG SNL day 1 |
Tet3 TDG |
Tet3 KD or TDG KD attenuates STAT3 induction in conditioned DRG | (Weng et al., 2017) |
| Tet3 | m6A tagging | mRNA | Adult DRG SNL |
– | Increase in m6A-tagged Tet3 mRNA after SNL, gained new m6A sites upon SNL | (Weng et al., 2018) |
| UHRF1 | microRNA | 3’UTR | Adult DRG SNL |
miR-9 | Gene induction after SNL, target of miR-9 | (Oh et al., 2018) |
| Vip | H4ac | Promoter | Adult DRG SNL |
HDACi (MS275) |
Gene induction HDAC1 inhibitor leads to H4ac enrichment and gene induction In N2A cells, pSmad1 promoter binding displaces HDAC1 |
(Finelli et al., 2013b) |
AV, adenovirus; HDACi: HDAC inhibitor; KD, knockdown; SNL, sciatic nerve lesion.