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Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE247320 | GEO | 2023/12/22

REPOSITORIES: GEO

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Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways.

Project description:Current treatments for neurodegenerative diseases and neural injuries face major challenges, primarily due to the diminished regenerative capacity of neurons in the mammalian CNS as they mature. Here, we investigated the role of Ezh2, a histone methyltransferase, in regulating mammalian axon regeneration. We found that Ezh2 declined in the mouse nervous system during maturation but was upregulated in adult dorsal root ganglion neurons following peripheral nerve injury to facilitate spontaneous axon regeneration. In addition, overexpression of Ezh2 in retinal ganglion cells in the CNS promoted optic nerve regeneration via both histone methylation-dependent and -independent mechanisms. Further investigation revealed that Ezh2 fostered axon regeneration by orchestrating the transcriptional silencing of genes governing synaptic function and those inhibiting axon regeneration, while concurrently activating various factors that support axon regeneration. Notably, we demonstrated that GABA transporter 2, encoded by Slc6a13, acted downstream of Ezh2 to control axon regeneration. Overall, our study underscores the potential of modulating chromatin accessibility as a promising strategy for promoting CNS axon regeneration.

| S-EPMC10849760 | biostudies-literature

Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways (RRBS)

Project description:Current treatments for neurodegenerative diseases and neural injuries fall short of success. One primary reason is that neurons in the mammalian central nervous system (CNS) lose their regeneration ability as they mature. Here, we investigated the role of Ezh2, a histone methyltransferase, in regulation of mammalian axon regeneration. We found that Ezh2 declined in the mouse nervous system during maturation but was upregulated in adult dorsal root ganglion neurons to support spontaneous axon regeneration following peripheral nerve injury. In addition, overexpression of Ezh2 in retinal ganglion cells in the CNS promoted optic nerve regeneration via both histone methylation-dependent and -independent mechanisms. Further investigation revealed that Ezh2 supported axon regeneration by systematically silencing the transcription of genes regulating synaptic function and inhibiting axon regeneration, while simultaneously activating various axon regeneration promoting factors. In particular, our study demonstrated that the GABA transporter 2 encoded by the gene Slc6a13 acted downstream of Ezh2 to control axon regeneration. Our study suggested that modulating chromatin accessibility was a promising strategy to promote CNS axon regeneration.

2023-12-22 | GSE247319 | GEO

Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways (ATAC-Seq)

2023-12-22 | GSE247315 | GEO

Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways (RNA-Seq II)

2023-12-22 | GSE247318 | GEO

Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways (RNA-Seq I)

2023-12-22 | GSE247317 | GEO

Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways

Project description:Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways

| PRJNA1037095 | ENA

Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways (RRBS)

Project description:Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways (RRBS)

| PRJNA1037107 | ENA

Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways (ATAC-Seq)

Project description:Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways (ATAC-Seq)

| PRJNA1037099 | ENA

Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways (RNA-Seq II)

Project description:Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways (RNA-Seq II)

| PRJNA1037100 | ENA

Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways (RNA-Seq I)

Project description:Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways (RNA-Seq I)

| PRJNA1037101 | ENA

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