Covalent modification of DNA regulates memory formation - PubMed (original) (raw)

Covalent modification of DNA regulates memory formation

Courtney A Miller et al. Neuron. 2007.

Free article

Erratum in

• Neuron. 2008 Sep 25;59(6):1051

Abstract

DNA methylation is a covalent chemical modification of DNA catalyzed by DNA methyltransferases (DNMTs). DNA methylation is associated with transcriptional silencing and has been studied extensively as a lifelong molecular information storage mechanism put in place during development. Here we report that DNMT gene expression is upregulated in the adult rat hippocampus following contextual fear conditioning and that DNMT inhibition blocks memory formation. In addition, fear conditioning is associated with rapid methylation and transcriptional silencing of the memory suppressor gene PP1 and demethylation and transcriptional activation of the synaptic plasticity gene reelin, indicating both methyltransferase and demethylase activity during consolidation. DNMT inhibition prevents the PP1 methylation increase, resulting in aberrant transcription of the gene during the memory-consolidation period. These results demonstrate that DNA methylation is dynamically regulated in the adult nervous system and that this cellular mechanism is a crucial step in memory formation.

PubMed Disclaimer

Similar articles

• Epigenetic regulation of reelin and brain-derived neurotrophic factor genes in long-term potentiation in rat medial prefrontal cortex.
  Sui L, Wang Y, Ju LH, Chen M. Sui L, et al. Neurobiol Learn Mem. 2012 May;97(4):425-40. doi: 10.1016/j.nlm.2012.03.007. Epub 2012 Mar 24. Neurobiol Learn Mem. 2012. PMID: 22469747
• DNA methylation and histone acetylation work in concert to regulate memory formation and synaptic plasticity.
  Miller CA, Campbell SL, Sweatt JD. Miller CA, et al. Neurobiol Learn Mem. 2008 May;89(4):599-603. doi: 10.1016/j.nlm.2007.07.016. Epub 2007 Sep 18. Neurobiol Learn Mem. 2008. PMID: 17881251 Free PMC article.
• Maternal Deprivation Enhances Contextual Fear Memory via Epigenetically Programming Second-Hit Stress-Induced Reelin Expression in Adult Rats.
  Wang RH, Chen YF, Chen S, Hao B, Xue L, Wang XG, Shi YW, Zhao H. Wang RH, et al. Int J Neuropsychopharmacol. 2018 Nov 1;21(11):1037-1048. doi: 10.1093/ijnp/pyy078. Int J Neuropsychopharmacol. 2018. PMID: 30169690 Free PMC article.
• The role of reelin in adult synaptic function and the genetic and epigenetic regulation of the reelin gene.
  Levenson JM, Qiu S, Weeber EJ. Levenson JM, et al. Biochim Biophys Acta. 2008 Aug;1779(8):422-31. doi: 10.1016/j.bbagrm.2008.01.001. Epub 2008 Jan 12. Biochim Biophys Acta. 2008. PMID: 18237558 Review.
• The human reelin gene: transcription factors (+), repressors (-) and the methylation switch (+/-) in schizophrenia.
  Grayson DR, Chen Y, Costa E, Dong E, Guidotti A, Kundakovic M, Sharma RP. Grayson DR, et al. Pharmacol Ther. 2006 Jul;111(1):272-86. doi: 10.1016/j.pharmthera.2005.01.007. Epub 2006 Mar 30. Pharmacol Ther. 2006. PMID: 16574235 Review.

Cited by

• Local chromatin microenvironment determines DNMT activity: from DNA methyltransferase to DNA demethylase or DNA dehydroxymethylase.
  van der Wijst MG, Venkiteswaran M, Chen H, Xu GL, Plösch T, Rots MG. van der Wijst MG, et al. Epigenetics. 2015;10(8):671-6. doi: 10.1080/15592294.2015.1062204. Epigenetics. 2015. PMID: 26098813 Free PMC article. Review.
• Integrative Transcriptome Profiling of Cognitive Aging and Its Preservation through Ser/Thr Protein Phosphatase Regulation.
  Park CS, Valomon A, Welzl H. Park CS, et al. PLoS One. 2015 Jun 23;10(6):e0130891. doi: 10.1371/journal.pone.0130891. eCollection 2015. PLoS One. 2015. PMID: 26102285 Free PMC article.
• Evidence from clinical and animal model studies of the long-term and transgenerational impact of stress on DNA methylation.
  Blaze J, Roth TL. Blaze J, et al. Semin Cell Dev Biol. 2015 Jul;43:76-84. doi: 10.1016/j.semcdb.2015.04.004. Epub 2015 Apr 23. Semin Cell Dev Biol. 2015. PMID: 25917771 Free PMC article. Review.
• Exploring epigenetic regulation of fear memory and biomarkers associated with post-traumatic stress disorder.
  Maddox SA, Schafe GE, Ressler KJ. Maddox SA, et al. Front Psychiatry. 2013 Jul 1;4:62. doi: 10.3389/fpsyt.2013.00062. eCollection 2013. Front Psychiatry. 2013. PMID: 23847551 Free PMC article.
• Histone acetylation: molecular mnemonics on the chromatin.
  Gräff J, Tsai LH. Gräff J, et al. Nat Rev Neurosci. 2013 Feb;14(2):97-111. doi: 10.1038/nrn3427. Epub 2013 Jan 17. Nat Rev Neurosci. 2013. PMID: 23324667 Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • H1 Connect
  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information

• Molecular Biology Databases

  • Gene Ontology