Skip to main content
SpringerLink
Log in

DNA Methylation in Memory Formation

  • Chapter
  • First Online:
Epigenetics, Brain and Behavior

Part of the book series: Research and Perspectives in Neurosciences ((NEUROSCIENCE))

Abstract

The mechanism by which behavioral memories are able to endure in a structure as dynamic as the brain is a long-standing mystery of cognition. For example, a memory must survive, by some mechanism, the ongoing replacement of the proteins that were initially responsible for its formation. In this review I describe the beginning of work designed to test the hypothesis that the brain utilizes DNA methylation as a mechanism to contribute to the stable maintenance of memories. Decades ago, both Francis Crick and Robin Holliday speculated that DNA methylation might be a self-perpetuating mechanism involved in memory storage. Ongoing studies in a number of laboratories are testing the idea that learning-induced epigenetic modifications in the cortex can serve as stable alterations in brain cells, contributing to the support of memory stability. Thinking in analogy to developmental biology, oncogenesis, and cellular differentiation, investigators in this area have begun to pursue the possibility that chromatin- and DNA-modifying molecular mechanisms might play a role in memory in the adult CNS.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alarcon JM, Malleret G, Touzani K, Vronskaya S, Ishii S, Kandel ER, Barco A (2004) Chromatin acetylation, memory, and LTP are impaired in CBP+/− mice. Neuron 42:947–959

    Article  PubMed  CAS  Google Scholar 

  • Barrett RM, Wood MA (2008) Beyond transcription factors: the role of chromatin modifying enzymes in regulating transcription required for memory. Learn Mem 15:460–467

    Article  PubMed  CAS  Google Scholar 

  • Beffert U, Weeber EJ, Durudas A, Qiu S, Masiulis I, Sweatt JD, Li WP, Adelmann G, Frotscher M, Hammer RE, Herz J. (2005) Modulation of synaptic plasticity and memory by Reelin involves differential splicing of the lipoprotein receptor Apoer2. Neuron 47(4):567–79

    Article  Google Scholar 

  • Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J, Zoghbi HY (2008) MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 320:1224–1229

    Article  PubMed  CAS  Google Scholar 

  • Collins AL, Levenson JM, Vilaythong AP, Richman R, Armstrong DL, Noebels JL, Sweatt JD, Zoghbi HY (2004) Mild overexpression of MeCP2 causes a progressive neurological disorder in mice. Hum Mol Genet 13:2679–2689

    Article  PubMed  CAS  Google Scholar 

  • Crick F (1984) Memory and molecular turnover. Nature 312:101

    Article  PubMed  CAS  Google Scholar 

  • Day JJ, Sweatt JD (2010) DNA methylation and memory formation. Nat Neurosci 13:1319–1323

    Article  PubMed  CAS  Google Scholar 

  • Feng J, Zhou Y, Campbell SL, Le T, Li E, Sweatt JD, Silva AJ, Fan G (2010) Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons. Nat Neurosci 13:423–430

    Article  PubMed  CAS  Google Scholar 

  • Frankland PW, Bontempi B, Talton LE, Kaczmarek L, Silva AJ (2004) The involvement of the anterior cingulate cortex in remote contextual fear memory. Science 304:881–883

    Article  PubMed  CAS  Google Scholar 

  • Graff J, Mansuy IM (2008) Epigenetic codes in cognition and behaviour. Behav Brain Res 192:70–87

    Article  PubMed  CAS  Google Scholar 

  • Holliday R (1999) Is there an epigenetic component in long-term memory? J Theor Biol 200:339–341

    Article  PubMed  CAS  Google Scholar 

  • Jiang Y, Langley B, Lubin FD, Renthal W, Wood MA, Yasui DH, Kumar A, Nestler EJ, Akbarian S, Beckel-Mitchener A (2008) Epigenetics in the nervous system. J Neurosci 28:11753–11759

    Article  PubMed  CAS  Google Scholar 

  • Kangaspeska S, Kangaspeska S, Stride B, Métivier R, Polycarpou-Schwarz M, Ibberson D, Carmouche RP, Benes V, Gannon F, Reid G (2008) Transient cyclical methylation of promoter DNA. Nature 452:112–115

    Article  PubMed  CAS  Google Scholar 

  • Kessels HW, Malinow R (2009) Synaptic AMPA receptor plasticity and behavior. Neuron 61:340–350

    Article  PubMed  CAS  Google Scholar 

  • Korzus E, Rosenfeld MG, Mayford M (2004) CBP histone acetyltransferase activity is a critical component of memory consolidation. Neuron 42:961–972

    Article  PubMed  CAS  Google Scholar 

  • Kriaucionis S, Heintz N (2009) The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science 324:929–930

    Article  PubMed  CAS  Google Scholar 

  • Levenson JM, Choi S, Lee SY, Cao YA, Ahn HJ, Worley KC, Pizzi M, Liou HC, Sweatt JD (2004) Regulation of histone acetylation during memory formation in the hippocampus. J Biol Chem 279:40545–40559

    Article  PubMed  CAS  Google Scholar 

  • Levenson JM, Roth TL, Lubin FD, Miller CA, Huang IC, Desai P, Malone LM, Sweatt JD (2006) Evidence that DNA (cytosine-5) methyltransferase regulates synaptic plasticity in the hippocampus. J Biol Chem 281:15763–15773

    Article  PubMed  CAS  Google Scholar 

  • Liu L, Van Groen T, Kadish I, Tollefsbol TO (2009) DNA methylation impacts on learning and memory in aging. Neurobiol Aging 30:549–560

    Article  PubMed  CAS  Google Scholar 

  • Lubin FD, Sweatt JD (2007) The IkappaB kinase regulates chromatin structure during reconsolidation of conditioned fear memories. Neuron 55:942–957

    Article  PubMed  CAS  Google Scholar 

  • Lubin FD, Roth TL, Sweatt JD (2008) Epigenetic regulation of bdnf gene transcription in the consolidation of fear memory. J Neurosci 28:10576–10586

    Article  PubMed  CAS  Google Scholar 

  • Ma DK, Guo JU, Ming GL, Song H (2009a) DNA excision repair proteins and Gadd45 as molecular players for active DNA demethylation. Cell Cycle 8:1526–1531

    Article  PubMed  CAS  Google Scholar 

  • Ma DK, Jang MH, Guo JU, Kitabatake Y, Chang ML, Pow-Anpongkul N, Flavell RA, Lu B, Ming GL, Song H (2009b) Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science 323:1074–1077

    Article  PubMed  CAS  Google Scholar 

  • Malleret G, Haditsch U, Genoux D, Jones MW, Bliss TV, Vanhoose AM, Weitlauf C, Kandel ER, Winder DG, Mansuy IM (2001) Inducible and reversible enhancement of learning, memory and long-term potentiation by inhibition of calcineurin. Cell 104:675–686

    PubMed  CAS  Google Scholar 

  • McCormack MG, Stornetta RL, Zhu JJ (2006) Synaptic AMPA receptor exchange maintains bidirectional plasticity. Neuron 60:75–88

    Article  Google Scholar 

  • Meaney MJ, Szyf M (2005a) Maternal care as a model for experience-dependent chromatin plasticity? Trends Neurosci 28:456–463

    Article  PubMed  CAS  Google Scholar 

  • Meaney MJ, Szyf M (2005b) Environmental programming of stress responses through DNA methylation: life at the interface between a dynamic environment and a fixed genome. Dialogues Clin Neurosci 7:103–123

    PubMed  Google Scholar 

  • Métivier R, Gallais R, Tiffoche C, Le Péron C, Jurkowska RZ, Carmouche RP, Ibberson D, Barath P, Demay F, Reid G, Benes V, Jeltsch A, Gannon F, Salbert G (2008) Cyclical DNA methylation of a transcriptionally active promoter. Nature 452:45–50

    Article  PubMed  Google Scholar 

  • Miller CA, Sweatt JD (2007) Covalent modification of DNA regulates memory formation. Neuron 53:857–869

    Article  PubMed  CAS  Google Scholar 

  • Miller CA, Campbell SL, Sweatt JD (2008) DNA methylation and histone acetylation work in concert to regulate memory formation and synaptic plasticity. Neurobiol Learn Mem 89:599–603

    Article  PubMed  CAS  Google Scholar 

  • Miller CA, Gavin CF, White JA, Parrish RR, Honasoge A, Yancey CR, Rivera IM, Rubio MD, Rumbaugh G, Sweatt JD (2010) Cortical DNA methylation maintains remote memory. Nat Neurosci 13:664–666

    Article  PubMed  CAS  Google Scholar 

  • Moretti P, Levenson JM, Battaglia F, Atkinson R, Teague R, Antalffy B, Armstrong D, Arancio O, Sweatt JD, Zoghbi HY (2006) Synaptic plasticity and learning and memory are impaired in a mouse model of Rett syndrome. J Neurosci 26:319–327

    Article  PubMed  CAS  Google Scholar 

  • Nelson ED, Kavalali ET, Monteggia LM (2008) Activity-dependent suppression of miniature neurotransmission through the regulation of DNA methylation. J Neurosci 28:395–406

    Article  PubMed  CAS  Google Scholar 

  • Ooi SK, Bestor TH (2008) The colorful history of active DNA demethylation. Cell 133:1145–1148

    Article  PubMed  CAS  Google Scholar 

  • Restivo L, Vetere G, Bontempi B, Ammassari-Teule M (2009) The formation of recent and remote memory is associated with time-dependent formation of spines in the hippocampus and anterior cingulate cortex. J Neurosci 29:8206–8214

    Article  PubMed  CAS  Google Scholar 

  • Roberson ED, Sweatt JD (1999) A biochemical blueprint for long-term memory. Learn Mem 6:381–388

    PubMed  CAS  Google Scholar 

  • Sanders MJ, Fanselow MS (2003) Pre-training prevents context fear conditioning deficits produced by hippocampal NDMA receptor blockade. Neurobiol Learn Mem 80:123–129

    Article  PubMed  CAS  Google Scholar 

  • Sweatt JD (2009) Experience-dependent epigenetic modifications in the central nervous system. Biol Psychiatry 65:191–197

    Article  PubMed  Google Scholar 

  • Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, Rao A (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324:930–935

    Article  PubMed  CAS  Google Scholar 

  • Wang SH, Teixeira CM, Wheeler AL, Frankland PW (2009) The precision of remote context memories does not require the hippocampus. Nat Neurosci 12:253–255

    Article  PubMed  Google Scholar 

  • Weaver IC, Champagne FA, Brown SE, Dymov S, Sharma S, Meaney MJ, Szyf M (2005) Reversal of maternal programming of stress responses in adult offspring through methyl supplementation: altering epigenetic marking later in life. J Neurosci 25:11045–11054

    Article  PubMed  CAS  Google Scholar 

  • Weeber EJ, Beffert U, Jones C, Christian JM, Forster E, Sweatt JD, Herz J (2002) Reelin and ApoE receptors cooperate to enhance synaptic plasticity and learning. J Biol Chem 277:39944–39952

    Article  PubMed  CAS  Google Scholar 

  • Wood MA, Attner MA, Oliveira AM, Brindle PK, Abel T (2006) A transcription factor-binding domain of the coactivator CBP is essential for long-term memory and the expression of specific target genes. Learn Mem 13:609–617

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurobiology and Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, 1825 University Blvd. SHEL 1010, Birmingham, AL, 35294-2182, USA

    J. David Sweatt Ph.D.

Authors
  1. J. David Sweatt Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. David Sweatt Ph.D. .

Editor information

Editors and Affiliations

  1. School of Medicine, Center for Metabolism and Epigenetics, University of California at Irvine, Sprague Hall 324, Irvine, 92697, California, USA

    Paolo Sassone Corsi

  2. Recherche Therapeutique, Fondation IPSEN pour la, quai George Gorse 65, Boulogne Billancourt Cedex, 92650, France

    Yves Christen

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Sweatt, J.D. (2012). DNA Methylation in Memory Formation. In: Sassone Corsi, P., Christen, Y. (eds) Epigenetics, Brain and Behavior. Research and Perspectives in Neurosciences. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27913-3_8

Download citation

Publish with us

Policies and ethics

Search

Navigation