PMID- 20006971 OWN - NLM STAT- MEDLINE DCOM- 20100504 LR - 20111117 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 166 IP - 1 DP - 2010 Mar 10 TI - Neuron-restrictive silencer factor causes epigenetic silencing of Kv4.3 gene after peripheral nerve injury. PG - 1-4 LID - 10.1016/j.neuroscience.2009.12.021 [doi] AB - Peripheral nerve injury causes a variety of alterations in pain-related gene expression in primary afferent, which underlie the neuronal plasticity in neuropathic pain. One of the characteristic alterations is a long-lasting downregulation of voltage-gated potassium (K(v)) channel, including K(v)4.3, in the dorsal root ganglion (DRG). The present study showed that nerve injury reduces the messenger RNA (mRNA) expression level of K(v)4.3 gene, which contains a conserved neuron-restrictive silencer element (NRSE), a binding site for neuron-restrictive silencer factor (NRSF). Moreover, we found that injury causes an increase in direct NRSF binding to K(v)4.3-NRSE in the DRG, using chromatin immunoprecipitation (ChIP) assay. ChIP assay further revealed that acetylation of histone H4, but not H3, at K(v)4.3-NRSE is markedly reduced at day 7 post-injury. Finally, the injury-induced K(v)4.3 downregulation was significantly blocked by antisense-knockdown of NRSF. Taken together, these data suggest that nerve injury causes an epigenetic silencing of K(v)4.3 gene mediated through transcriptional suppressor NRSF in the DRG. CI - Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Uchida, H AU - Uchida H AD - Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. FAU - Sasaki, K AU - Sasaki K FAU - Ma, L AU - Ma L FAU - Ueda, H AU - Ueda H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20091213 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Histones) RN - 0 (Oligonucleotides, Antisense) RN - 0 (RE1-silencing transcription factor) RN - 0 (RNA, Messenger) RN - 0 (Repressor Proteins) RN - 0 (Shal Potassium Channels) SB - IM MH - Animals MH - Disease Models, Animal MH - Down-Regulation/physiology MH - Epigenesis, Genetic/*physiology MH - Ganglia, Spinal/metabolism/physiopathology MH - Gene Expression Regulation/physiology MH - Gene Silencing/*physiology MH - Histones/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Neuralgia/genetics/metabolism/physiopathology MH - Oligonucleotides, Antisense/pharmacology MH - Peripheral Nerve Injuries MH - Peripheral Nerves/metabolism/physiopathology MH - Peripheral Nervous System Diseases/*genetics/metabolism/physiopathology MH - Protein Binding/genetics MH - RNA, Messenger/metabolism MH - Repressor Proteins/*genetics/metabolism MH - Sensory Receptor Cells/metabolism MH - Shal Potassium Channels/*genetics/metabolism MH - Silencer Elements, Transcriptional/genetics EDAT- 2009/12/17 06:00 MHDA- 2010/05/05 06:00 CRDT- 2009/12/17 06:00 PHST- 2009/11/13 00:00 [received] PHST- 2009/12/04 00:00 [revised] PHST- 2009/12/07 00:00 [accepted] PHST- 2009/12/17 06:00 [entrez] PHST- 2009/12/17 06:00 [pubmed] PHST- 2010/05/05 06:00 [medline] AID - S0306-4522(09)02056-9 [pii] AID - 10.1016/j.neuroscience.2009.12.021 [doi] PST - ppublish SO - Neuroscience. 2010 Mar 10;166(1):1-4. doi: 10.1016/j.neuroscience.2009.12.021. Epub 2009 Dec 13.