| Title: |
Epigenetic regulator UHRF1 inactivates REST and growth suppressor gene expression via DNA methylation to promote axon regeneration. |
| Authors: |
Young Mi Oh, Mahar, Marcus, Ewan, Eric E., Leahy, Kathleen M., Guoyan Zhao, Cavalli, Valeria |
| Source: |
Proceedings of the National Academy of Sciences of the United States of America; 12/26/2018, Vol. 115 Issue 52, pE12417-E12426, 10p |
| Subject Terms: |
DNA methylation, AXONS, EPIGENETICS, GENETIC regulation, METHYLTRANSFERASE genetics, GENE expression, CENTRAL nervous system injuries, DORSAL root ganglia |
| Abstract: |
Injured peripheral sensory neurons switch to a regenerative state after axon injury, which requires transcriptional and epigenetic changes. However, the roles and mechanisms of gene inactivation after injury are poorly understood. Here, we show that DNA methylation, which generally leads to gene silencing, is required for robust axon regeneration after peripheral nerve lesion. Ubiquitinlike containing PHD ring finger 1 (UHRF1), a critical epigenetic regulator involved inDNAmethylation, increases upon axon injury and is required for robust axon regeneration. The increased level of UHRF1 results from a decrease in miR-9. The level of another target of miR-9, the transcriptional regulator RE1 silencing transcription factor (REST), transiently increases after injury and is required for axon regeneration. Mechanistically, UHRF1 interacts with DNA methyltransferases (DNMTs) and H3K9me3 at the promoter region to repress the expression of the tumor suppressor gene phosphatase andtensinhomolog(PTEN) andREST.Our study reveals an epigenetic mechanism that silences tumor suppressor genes and restricts REST expression in time after injury to promote axon regeneration. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
