Skip to main content
SpringerLink
Log in

Rubinstein-Taybi Syndrome and Epigenetic Alterations

  • Chapter
  • First Online:
Neuroepigenomics in Aging and Disease

Part of the book series: Advances in Experimental Medicine and Biology ((PMISB,volume 978))

Abstract

Rubinstein-Taybi syndrome (RSTS) is a rare genetic disorder in humans characterized by growth and psychomotor delay, abnormal gross anatomy, and mild to severe mental retardation (Rubinstein and Taybi, Am J Dis Child 105:588–608, 1963, Hennekam et al., Am J Med Genet Suppl 6:56–64, 1990). RSTS is caused by de novo mutations in epigenetics-associated genes, including the cAMP response element-binding protein (CREBBP), the gene-encoding protein referred to as CBP, and the EP300 gene, which encodes the p300 protein, a CBP homologue. Recent studies of the epigenetic mechanisms underlying cognitive functions in mice provide direct evidence for the involvement of nuclear factors (e.g., CBP) in the control of higher cognitive functions. In fact, a role for CBP in higher cognitive function is suggested by the finding that RSTS is caused by heterozygous mutations at the CBP locus (Petrij et al., Nature 376:348–351, 1995). CBP was demonstrated to possess an intrinsic histone acetyltransferase activity (Ogryzko et al., Cell 87:953–959, 1996) that is required for CREB-mediated gene expression (Korzus et al., Science 279:703–707, 1998). The intrinsic protein acetyltransferase activity in CBP might directly destabilize promoter-bound nucleosomes, facilitating the activation of transcription. Due to the complexity of developmental abnormalities and the possible genetic compensation associated with this congenital disorder, however, it is difficult to establish a direct role for CBP in cognitive function in the adult brain. Although aspects of the clinical presentation in RSTS cases have been extensively studied, a spectrum of symptoms found in RSTS patients can be accessed only after birth, and, thus, prenatal genetic tests for this extremely rare genetic disorder are seldom considered. Even though there has been intensive research on the genetic and epigenetic function of the CREBBP gene in rodents, the etiology of this devastating congenital human disorder is largely unknown.

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 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 279.99
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

  1. Rosenfeld MG, Glass CK. Coregulator codes of transcriptional regulation by nuclear receptors. J Biol Chem. 2001;276(40):36865–8.

    Article  CAS  PubMed  Google Scholar 

  2. Neely KE, Workman JL. Histone acetylation and chromatin remodeling: which comes first? Mol Genet Metab. 2002;76(1):1–5.

    Article  CAS  PubMed  Google Scholar 

  3. Fischle W, Wang Y, Allis CD. Histone and chromatin cross-talk. Curr Opin Cell Biol. 2003;15(2):172–83.

    Article  CAS  PubMed  Google Scholar 

  4. Chrivia JC, Kwok RP, Lamb N, Hagiwara M, Montminy MR, Goodman RH. Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature. 1993;365(6449):855–9.

    Article  CAS  PubMed  Google Scholar 

  5. Eckner R, Ewen ME, Newsome D, Gerdes M, DeCaprio JA, Lawrence JB, Livingston DM. Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor. Genes Dev. 1994;8(8):869–84.

    Article  CAS  PubMed  Google Scholar 

  6. Janknecht R. The versatile functions of the transcriptional coactivators p300 and CBP and their roles in disease. Histol Histopathol. 2002;17(2):657–68.

    CAS  PubMed  Google Scholar 

  7. Allis CD, Berger SL, Cote J, Dent S, Jenuwien T, Kouzarides T, Pillus L, Reinberg D, Shi Y, Shiekhattar R, Shilatifard A, Workman J, Zhang Y. New nomenclature for chromatin-modifying enzymes. Cell. 2007;131(4):633–6.

    Article  CAS  PubMed  Google Scholar 

  8. Chan HM, La Thangue NB. p300/CBP proteins: HATs for transcriptional bridges and scaffolds. J Cell Sci. 2001;114(Pt 13):2363–73.

    CAS  PubMed  Google Scholar 

  9. Wang F, Marshall CB, Ikura M. Transcriptional/epigenetic regulator CBP/p300 in tumorigenesis: structural and functional versatility in target recognition. Cell Mol Life Sci. 2013;70(21):3989–4008.

    Article  CAS  PubMed  Google Scholar 

  10. Ogryzko VV, Schiltz RL, Russanova V, Howard BH, Nakatani Y. The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell. 1996;87(5):953–9.

    Article  CAS  PubMed  Google Scholar 

  11. Yuan LW, Soh JW, Weinstein IB. Inhibition of histone acetyltransferase function of p300 by PKCdelta. Biochim Biophys Acta. 2002;1592(2):205–11.

    Article  CAS  PubMed  Google Scholar 

  12. Korzus E, Torchia J, Rose DW, Xu L, Kurokawa R, McInerney EM, Mullen TM, Glass CK, Rosenfeld MG. Transcription factor-specific requirements for coactivators and their acetyltransferase functions. Science. 1998;279(5351):703–7.

    Article  CAS  PubMed  Google Scholar 

  13. Puri PL, Avantaggiati ML, Balsano C, Sang N, Graessmann A, Giordano A, Levrero M. p300 is required for MyoD-dependent cell cycle arrest and muscle-specific gene transcription. EMBO J. 1997;16(2):369–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Korzus E, Rosenfeld MG, Mayford M. CBP histone acetyltransferase activity is a critical component of memory consolidation. Neuron. 2004;42(6):961–72.

    Article  CAS  PubMed  Google Scholar 

  15. Lopez-Atalaya JP, Valor LM, Barco A. Epigenetic factors in intellectual disability: the Rubinstein-Taybi syndrome as a paradigm of neurodevelopmental disorder with epigenetic origin. Prog Mol Biol Transl Sci. 2014;128:139–76.

    Article  CAS  PubMed  Google Scholar 

  16. Oliveira AM, Abel T, Brindle PK, Wood MA. Differential role for CBP and p300 CREB-binding domain in motor skill learning. Behav Neurosci. 2006;120(3):724–9.

    Article  CAS  PubMed  Google Scholar 

  17. Rubinstein JH, Taybi H. Broad thumbs and toes and facial abnormalities. Am J Dis Child. 1963;105:588–608.

    Article  CAS  PubMed  Google Scholar 

  18. Hennekam RC, Stevens CA, Van de Kamp JJ. Etiology and recurrence risk in Rubinstein-Taybi syndrome. Am J Med Genet Suppl. 1990;6:56–64.

    CAS  PubMed  Google Scholar 

  19. Petrij F, Giles RH, Dauwerse HG, Saris JJ, Hennekam RC, Masuno M, Tommerup N, van Ommen GJ, Goodman RH, Peters DJ, et al. Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature. 1995;376(6538):348–51.

    Article  CAS  PubMed  Google Scholar 

  20. LOVD v.2.0: the next generation in gene variant databases (Updated February 12, 2016) [Internet]. Wiley-Liss, Inc. 2011. http://www.LOVD.nl.

  21. CREBBP [Internet]. Jean-Loup Huret (Editor-in-Chief); INIST-CNRS (Publisher). 2010. http://atlasgeneticsoncology.org//Genes/CBPID42.html.

  22. Coupry I, Roudaut C, Stef M, Delrue MA, Marche M, Burgelin I, Taine L, Cruaud C, Lacombe D, Arveiler B. Molecular analysis of the CBP gene in 60 patients with Rubinstein-Taybi syndrome. J Med Genet. 2002;39(6):415–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bentivegna A, Milani D, Gervasini C, Castronovo P, Mottadelli F, Manzini S, Colapietro P, Giordano L, Atzeri F, Divizia MT, Uzielli ML, Neri G, Bedeschi MF, Faravelli F, Selicorni A, Larizza L. Rubinstein-Taybi syndrome: spectrum of CREBBP mutations in Italian patients. BMC Med Genet. 2006;7:77.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Roelfsema JH, White SJ, Ariyurek Y, Bartholdi D, Niedrist D, Papadia F, Bacino CA, den Dunnen JT, van Ommen GJ, Breuning MH, Hennekam RC, Peters DJ. Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease. Am J Hum Genet. 2005;76(4):572–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Negri G, Magini P, Milani D, Colapietro P, Rusconi D, Scarano E, Bonati MT, Priolo M, Crippa M, Mazzanti L, Wischmeijer A, Tamburrino F, Pippucci T, Finelli P, Larizza L, Gervasini C. From whole gene deletion to point mutations of EP300-positive Rubinstein-Taybi patients: new insights into the mutational spectrum and peculiar clinical hallmarks. Hum Mutat. 2016;37(2):175–83.

    Article  CAS  PubMed  Google Scholar 

  26. Spena S, Milani D, Rusconi D, Negri G, Colapietro P, Elcioglu N, Bedeschi F, Pilotta A, Spaccini L, Ficcadenti A, Magnani C, Scarano G, Selicorni A, Larizza L, Gervasini C. Insights into genotype-phenotype correlations from CREBBP point mutation screening in a cohort of 46 Rubinstein-Taybi syndrome patients. Clin Genet. 2015;88(5):431–40.

    Article  CAS  PubMed  Google Scholar 

  27. van Belzen M, Bartsch O, Lacombe D, Peters DJ, Hennekam RC. Rubinstein-Taybi syndrome (CREBBP, EP300). Eur J Hum Genet. 2011;19(1):121.

    Article  Google Scholar 

  28. Fergelot P, Van Belzen M, Van Gils J, Afenjar A, Armour CM, Arveiler B, Beets L, Burglen L, Busa T, Collet M, Deforges J, de Vries BB, Dominguez Garrido E, Dorison N, Dupont J, Francannet C, Garcia-Minaur S, Gabau Vila E, Gebre-Medhin S, Gener Querol B, Genevieve D, Gerard M, Gervasini CG, Goldenberg A, Josifova D, Lachlan K, Maas S, Maranda B, Moilanen JS, Nordgren A, Parent P, Rankin J, Reardon W, Rio M, Roume J, Shaw A, Smigiel R, Sojo A, Solomon B, Stembalska A, Stumpel C, Suarez F, Terhal P, Thomas S, Touraine R, Verloes A, Vincent-Delorme C, Wincent J, Peters DJ, Bartsch O, Larizza L, Lacombe D, Hennekam RC. Phenotype and genotype in 52 patients with Rubinstein-Taybi syndrome caused by EP300 mutations. Am J Med Genet A. 2016;170(12):3069–82.

    Article  CAS  PubMed  Google Scholar 

  29. Kwok RP, Lundblad JR, Chrivia JC, Richards JP, Bachinger HP, Brennan RG, Roberts SG, Green MR, Goodman RH. Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature. 1994;370(6486):223–6.

    Article  CAS  PubMed  Google Scholar 

  30. Cardinaux JR, Notis JC, Zhang Q, Vo N, Craig JC, Fass DM, Brennan RG, Goodman RH. Recruitment of CREB binding protein is sufficient for CREB-mediated gene activation. Mol Cell Biol. 2000;20(5):1546–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Bedford DC, Kasper LH, Fukuyama T, Brindle PK. Target gene context influences the transcriptional requirement for the KAT3 family of CBP and p300 histone acetyltransferases. Epigenetics. 2010;5(1):9–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Shiama N. The p300/CBP family: integrating signals with transcription factors and chromatin. Trends Cell Biol. 1997;7(6):230–6.

    Article  CAS  PubMed  Google Scholar 

  33. Goodman RH, Smolik S. CBP/p300 in cell growth, transformation, and development. Genes Dev. 2000;14(13):1553–77.

    CAS  PubMed  Google Scholar 

  34. De Guzman RN, Martinez-Yamout MA, Dyson HJ, Wright PE. Structure and function of the CBP/p300 TAZ domains. In: Iuchi S, Kuldell N, editors. Zinc finger proteins: from atomic contact to cellular function. Molecular biology intelligence unit. Georgetown, TX, New York: Landes Bioscience; Kluwer Academic/Plenum; 2005.

    Google Scholar 

  35. Demarest SJ, Martinez-Yamout M, Chung J, Chen H, Xu W, Dyson HJ, Evans RM, Wright PE. Mutual synergistic folding in recruitment of CBP/p300 by p160 nuclear receptor coactivators. Nature. 2002;415(6871):549–53.

    Article  CAS  PubMed  Google Scholar 

  36. Bannister AJ, Kouzarides T. The CBP co-activator is a histone acetyltransferase. Nature. 1996;384(6610):641–3.

    Article  CAS  PubMed  Google Scholar 

  37. Brownell JE, Allis CD. Special HATs for special occasions: linking histone acetylation to chromatin assembly and gene activation. Curr Opin Genet Dev. 1996;6(2):176–84.

    Article  CAS  PubMed  Google Scholar 

  38. Wong MM, Byun JS, Sacta M, Jin Q, Baek S, Gardner K. Promoter-bound p300 complexes facilitate post-mitotic transmission of transcriptional memory. PLoS One. 2014;9(6):e99989.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Das C, Lucia MS, Hansen KC, Tyler JK. CBP/p300-mediated acetylation of histone H3 on lysine 56. Nature. 2009;459(7243):113–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Jin Q, Yu LR, Wang L, Zhang Z, Kasper LH, Lee JE, Wang C, Brindle PK, Dent SY, Ge K. Distinct roles of GCN5/PCAF-mediated H3K9ac and CBP/p300-mediated H3K18/27ac in nuclear receptor transactivation. EMBO J. 2011;30(2):249–62.

    Article  CAS  PubMed  Google Scholar 

  41. McManus KJ, Hendzel MJ. Quantitative analysis of CBP- and P300-induced histone acetylations in vivo using native chromatin. Mol Cell Biol. 2003;23(21):7611–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Tanaka Y, Naruse I, Maekawa T, Masuya H, Shiroishi T, Ishii S. Abnormal skeletal patterning in embryos lacking a single Cbp allele: a partial similarity with Rubinstein-Taybi syndrome. Proc Natl Acad Sci U S A. 1997;94(19):10215–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Oike Y, Hata A, Mamiya T, Kaname T, Noda Y, Suzuki M, Yasue H, Nabeshima T, Araki K, Yamamura K. Truncated CBP protein leads to classical Rubinstein-Taybi syndrome phenotypes in mice: implications for a dominant-negative mechanism. Hum Mol Genet. 1999;8(3):387–96.

    Article  CAS  PubMed  Google Scholar 

  44. Oike Y, Takakura N, Hata A, Kaname T, Akizuki M, Yamaguchi Y, Yasue H, Araki K, Yamamura K, Suda T. Mice homozygous for a truncated form of CREB-binding protein exhibit defects in hematopoiesis and vasculo-angiogenesis. Blood. 1999;93(9):2771–9.

    CAS  PubMed  Google Scholar 

  45. Tanaka Y, Naruse I, Hongo T, Xu M, Nakahata T, Maekawa T, Ishii S. Extensive brain hemorrhage and embryonic lethality in a mouse null mutant of CREB-binding protein. Mech Dev. 2000;95(1–2):133–45.

    Article  CAS  PubMed  Google Scholar 

  46. Yao TP, Oh SP, Fuchs M, Zhou ND, Ch'ng LE, Newsome D, Bronson RT, Li E, Livingston DM, Eckner R. Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. Cell. 1998;93(3):361–72.

    Article  CAS  PubMed  Google Scholar 

  47. Squire LR. Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans [published erratum appears in Psychol Rev 1992 Jul;99(3):582]. Psychol Rev. 1992;99(2):195–231.

    Article  CAS  PubMed  Google Scholar 

  48. McGaugh JL, Hertz MJ. Memory consolidation. San Francisco: Albion; 1972.

    Google Scholar 

  49. Squire LR. Memory and brain. New York: Oxford; 1987.

    Google Scholar 

  50. Andrew RJ. The functional organization of phases of memory consolidation. In: Hinde RA, Beer C, Bunsel M, editors. Advances in the study of behaviour, vol. 11. New York: Academic; 1980. p. 337–67.

    Google Scholar 

  51. Davis HP, Squire LR. Protein synthesis and memory: a review. Psychol Bull. 1984;96(3):518–59.

    Article  CAS  PubMed  Google Scholar 

  52. Worley PF, Cole AJ, Murphy TH, Christy BA, Nakabeppu Y, Baraban JM. Synaptic regulation of immediate-early genes in brain. Cold Spring Harb Symp Quant Biol. 1990;55:213–23.

    Article  CAS  PubMed  Google Scholar 

  53. Tischmeyer W, Grimm R. Activation of immediate early genes and memory formation. Cell Mol Life Sci. 1999;55(4):564–74.

    Article  CAS  PubMed  Google Scholar 

  54. Bourtchuladze R, Frenguelli B, Blendy J, Cioffi D, Schutz G, Silva AJ. Deficient long-term memory in mice with a targeted mutation of the cAMP- responsive element-binding protein. Cell. 1994;79(1):59–68.

    Article  CAS  PubMed  Google Scholar 

  55. Pittenger C, Huang YY, Paletzki RF, Bourtchouladze R, Scanlin H, Vronskaya S, Kandel ER. Reversible inhibition of CREB/ATF transcription factors in region CA1 of the dorsal hippocampus disrupts hippocampus-dependent spatial memory. Neuron. 2002;34(3):447–62.

    Article  CAS  PubMed  Google Scholar 

  56. Jones MW, Errington ML, French PJ, Fine A, Bliss TV, Garel S, Charnay P, Bozon B, Laroche S, Davis S. A requirement for the immediate early gene Zif268 in the expression of late LTP and long-term memories. Nat Neurosci. 2001;4(3):289–96.

    Article  CAS  PubMed  Google Scholar 

  57. Josselyn SA, Shi C, Carlezon Jr WA, Neve RL, Nestler EJ, Davis M. Long-term memory is facilitated by cAMP response element-binding protein overexpression in the amygdala. J Neurosci. 2001;21(7):2404–12.

    CAS  PubMed  Google Scholar 

  58. Fleischmann A, Hvalby O, Jensen V, Strekalova T, Zacher C, Layer LE, Kvello A, Reschke M, Spanagel R, Sprengel R, Wagner EF, Gass P. Impaired long-term memory and NR2A-type NMDA receptor-dependent synaptic plasticity in mice lacking c-Fos in the CNS. J Neurosci. 2003;23(27):9116–22.

    CAS  PubMed  Google Scholar 

  59. Kida S, Josselyn SA, de Ortiz SP, Kogan JH, Chevere I, Masushige S, Silva AJ. CREB required for the stability of new and reactivated fear memories. Nat Neurosci. 2002;5(4):348–55.

    Article  CAS  PubMed  Google Scholar 

  60. Brindle PK, Montminy MR. The CREB family of transcription activators. Curr Opin Genet Dev. 1992;2(2):199–204.

    Article  CAS  PubMed  Google Scholar 

  61. Gonzalez GA, Montminy MR. Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell. 1989;59(4):675–80.

    Article  CAS  PubMed  Google Scholar 

  62. Gonzalez GA, Yamamoto KK, Fischer WH, Karr D, Menzel P, Biggs 3rd W, Vale WW, Montminy MR. A cluster of phosphorylation sites on the cyclic AMP-regulated nuclear factor CREB predicted by its sequence. Nature. 1989;337(6209):749–52.

    Article  CAS  PubMed  Google Scholar 

  63. Deisseroth K, Bito H, Tsien RW. Signaling from synapse to nucleus: postsynaptic CREB phosphorylation during multiple forms of hippocampal synaptic plasticity. Neuron. 1996;16(1):89–101.

    Article  CAS  PubMed  Google Scholar 

  64. Byrne JH, Kandel ER. Presynaptic facilitation revisited: state and time dependence. J Neurosci. 1996;16(2):425–35.

    CAS  PubMed  Google Scholar 

  65. Castellucci VF, Kandel ER, Schwartz JH, Wilson FD, Nairn AC, Greengard P. Intracellular injection of t he catalytic subunit of cyclic AMP- dependent protein kinase simulates facilitation of transmitter release underlying behavioral sensitization in Aplysia. Proc Natl Acad Sci U S A. 1980;77(12):7492–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Castellucci VF, Nairn A, Greengard P, Schwartz JH, Kandel ER. Inhibitor of adenosine 3':5'-monophosphate-dependent protein kinase blocks presynaptic facilitation in Aplysia. J Neurosci. 1982;2(12):1673–81.

    CAS  PubMed  Google Scholar 

  67. Abel T, Martin KC, Bartsch D, Kandel ER. Memory suppressor genes: inhibitory constraints on the storage of long- term memory. Science. 1998;279(5349):338–41.

    Article  CAS  PubMed  Google Scholar 

  68. Alberini CM, Ghirardi M, Metz R, Kandel ER. C/EBP is an immediate-early gene required for the consolidation of long- term facilitation in Aplysia. Cell. 1994;76(6):1099–114.

    Article  CAS  PubMed  Google Scholar 

  69. Bartsch D, Casadio A, Karl KA, Serodio P, Kandel ER. CREB1 encodes a nuclear activator, a repressor, and a cytoplasmic modulator that form a regulatory unit critical for long-term facilitation. Cell. 1998;95(2):211–23.

    Article  CAS  PubMed  Google Scholar 

  70. Bartsch D, Ghirardi M, Skehel PA, Karl KA, Herder SP, Chen M, Bailey CH, Kandel ER. Aplysia CREB2 represses long-term facilitation: relief of repression converts transient facilitation into long-term functional and structural change. Cell. 1995;83(6):979–92.

    Article  CAS  PubMed  Google Scholar 

  71. Yin JC, Wallach JS, Del Vecchio M, Wilder EL, Zhou H, Quinn WG, Tully T. Induction of a dominant negative CREB transgene specifically blocks long-term memory in Drosophila. Cell. 1994;79(1):49–58.

    Article  CAS  PubMed  Google Scholar 

  72. Bliss TV, Gardner-Medwin AR. Long-lasting potentiation of synaptic transmission in the dentate area of the unanaestetized rabbit following stimulation of the perforant path. J Physiol (Lond). 1973;232(2):357–74.

    Article  CAS  Google Scholar 

  73. Bliss TV, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993;361(6407):31–9.

    Article  CAS  PubMed  Google Scholar 

  74. Bliss TV, Richter-Levin G. Spatial learning and the saturation of long-term potentiation [comment]. Hippocampus. 1993;3(2):123–5.

    Article  CAS  PubMed  Google Scholar 

  75. Malenka RC. Synaptic plasticity in the hippocampus: LTP and LTD. Cell. 1994;78(4):535–8.

    Article  CAS  PubMed  Google Scholar 

  76. Collingridge GL, Kehl SJ, McLennan H. The antagonism of amino acid-induced excitations of rat hippocampal CA1 neurones in vitro. J Physiol (Lond). 1983;334:19–31.

    Article  CAS  Google Scholar 

  77. Dudek SM, Bear MF. Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-D-aspartate receptor blockade. Proc Natl Acad Sci U S A. 1992;89(10):4363–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Davis S, Butcher SP, Morris RG. The NMDA receptor antagonist D-2-amino-5-phosphonopentanoate (D-AP5) impairs spatial learning and LTP in vivo at intracerebral concentrations comparable to those that block LTP in vitro. J Neurosci. 1992;12(1):21–34.

    CAS  PubMed  Google Scholar 

  79. Abeliovich A, Chen C, Goda Y, Silva AJ, Stevens CF, Tonegawa S. Modified hippocampal long-term potentiation in PKC gamma-mutant mice. Cell. 1993;75(7):1253–62.

    Article  CAS  PubMed  Google Scholar 

  80. Abeliovich A, Paylor R, Chen C, Kim JJ, Wehner JM, Tonegawa S. PKC gamma mutant mice exhibit mild deficits in spatial and contextual learning. Cell. 1993;75(7):1263–71.

    Article  CAS  PubMed  Google Scholar 

  81. Grant SG, O'Dell TJ, Karl KA, Stein PL, Soriano P, Kandel ER. Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice [see comments]. Science. 1992;258(5090):1903–10.

    Article  CAS  PubMed  Google Scholar 

  82. Sakimura K, Kutsuwada T, Ito I, Manabe T, Takayama C, Kushiya E, Yagi T, Aizawa S, Inoue Y, Sugiyama H, et al. Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor epsilon 1 subunit. Nature. 1995;373(6510):151–5.

    Article  CAS  PubMed  Google Scholar 

  83. Silva AJ, Stevens CF, Tonegawa S, Wang Y. Deficient hippocampal long-term potentiation in alpha-calcium- calmodulin kinase II mutant mice. Science. 1992;257(5067):201–6.

    Article  CAS  PubMed  Google Scholar 

  84. Silva AJ, Wang Y, Paylor R, Wehner JM, Stevens CF, Tonegawa S. Alpha calcium/calmodulin kinase II mutant mice: deficient long-term potentiation and impaired spatial learning. Cold Spring Harb Symp Quant Biol. 1992;57:527–39.

    Article  CAS  PubMed  Google Scholar 

  85. Hardingham GE, Chawla S, Cruzalegui FH, Bading H. Control of recruitment and transcription-activating function of CBP determines gene regulation by NMDA receptors and L-type calcium channels. Neuron. 1999;22(4):789–98.

    Article  CAS  PubMed  Google Scholar 

  86. Hu SC, Chrivia J, Ghosh A. Regulation of CBP-mediated transcription by neuronal calcium signaling. Neuron. 1999;22(4):799–808.

    Article  CAS  PubMed  Google Scholar 

  87. Impey S, Fong AL, Wang Y, Cardinaux JR, Fass DM, Obrietan K, Wayman GA, Storm DR, Soderling TR, Goodman RH. Phosphorylation of CBP mediates transcriptional activation by neural activity and CaM kinase IV. Neuron. 2002;34(2):235–44.

    Article  CAS  PubMed  Google Scholar 

  88. Guan Z, Giustetto M, Lomvardas S, Kim JH, Miniaci MC, Schwartz JH, Thanos D, Kandel ER. Integration of long-term-memory-related synaptic plasticity involves bidirectional regulation of gene expression and chromatin structure. Cell. 2002;111(4):483–93.

    Article  CAS  PubMed  Google Scholar 

  89. Malenka RC, Nicoll RA. Long-term potentiation—a decade of progress? Science. 1999;285(5435):1870–4.

    Article  CAS  PubMed  Google Scholar 

  90. Tsien JZ, Huerta PT, Tonegawa S. The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory. Cell. 1996;87(7):1327–38.

    Article  CAS  PubMed  Google Scholar 

  91. Morris RG, Anderson E, Lynch GS, Baudry M. Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature. 1986;319(6056):774–6.

    Article  CAS  PubMed  Google Scholar 

  92. Alarcon JM, Malleret G, Touzani K, Vronskaya S, Ishii S, Kandel ER, Barco A. Chromatin acetylation, memory, and LTP are impaired in CBP+/− mice: a model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration. Neuron. 2004;42(6):947–59.

    Article  CAS  PubMed  Google Scholar 

  93. Wood MA, Kaplan MP, Park A, Blanchard EJ, Oliveira AM, Lombardi TL, Abel T. Transgenic mice expressing a truncated form of CREB-binding protein (CBP) exhibit deficits in hippocampal synaptic plasticity and memory storage. Learn Mem. 2005;12(2):111–9.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Wood MA, Attner MA, Oliveira AM, Brindle PK, Abel T. A transcription factor-binding domain of the coactivator CBP is essential for long-term memory and the expression of specific target genes. Learn Mem. 2006;13(5):609–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Barrett RM, Malvaez M, Kramar E, Matheos DP, Arrizon A, Cabrera SM, Lynch G, Greene RW, Wood MA. Hippocampal focal knockout of CBP affects specific histone modifications, long-term potentiation, and long-term memory. Neuropsychopharmacology. 2011;36(8):1545–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Valor LM, Pulopulos MM, Jimenez-Minchan M, Olivares R, Lutz B, Barco A. Ablation of CBP in forebrain principal neurons causes modest memory and transcriptional defects and a dramatic reduction of histone acetylation but does not affect cell viability. J Neurosci. 2011;31(5):1652–63.

    Article  CAS  PubMed  Google Scholar 

  97. Levenson JM, Sweatt JD. Epigenetic mechanisms: a common theme in vertebrate and invertebrate memory formation. Cell Mol Life Sci. 2006;63(9):1009–16.

    Article  CAS  PubMed  Google Scholar 

  98. Vieira PA, Korzus E. CBP-dependent memory consolidation in the prefrontal cortex supports object-location learning. Hippocampus. 2015;25(12):1532–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Vieira PA, Lovelace JW, Corches A, Rashid AJ, Josselyn SA, Korzus E. Prefrontal consolidation supports the attainment of fear memory accuracy. Learn Mem. 2014;21(8):394–405.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Lopez-Atalaya JP, Ciccarelli A, Viosca J, Valor LM, Jimenez-Minchan M, Canals S, Giustetto M, Barco A. CBP is required for environmental enrichment-induced neurogenesis and cognitive enhancement. EMBO J. 2011;30(20):4287–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Kasper LH, Boussouar F, Ney PA, Jackson CW, Rehg J, van Deursen JM, Brindle PK. A transcription-factor-binding surface of coactivator p300 is required for haematopoiesis. Nature. 2002;419(6908):738–43.

    Article  CAS  PubMed  Google Scholar 

  102. Vecsey CG, Hawk JD, Lattal KM, Stein JM, Fabian SA, Attner MA, Cabrera SM, McDonough CB, Brindle PK, Abel T, Wood MA. Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB:CBP-dependent transcriptional activation. J Neurosci. 2007;27(23):6128–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Maddox SA, Watts CS, Schafe GE. p300/CBP histone acetyltransferase activity is required for newly acquired and reactivated fear memories in the lateral amygdala. Learn Mem. 2013;20(2):109–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Stafford JM, Raybuck JD, Ryabinin AE, Lattal KM. Increasing histone acetylation in the hippocampus-infralimbic network enhances fear extinction. Biol Psychiatry. 2012;72(1):25–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Bredy TW, Wu H, Crego C, Zellhoefer J, Sun YE, Barad M. Histone modifications around individual BDNF gene promoters in prefrontal cortex are associated with extinction of conditioned fear. Learn Mem. 2007;14(4):268–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Lattal KM, Barrett RM, Wood MA. Systemic or intrahippocampal delivery of histone deacetylase inhibitors facilitates fear extinction. Behav Neurosci. 2007;121(5):1125–31.

    Article  CAS  PubMed  Google Scholar 

  107. Aimone JB, Deng W, Gage FH. Resolving new memories: a critical look at the dentate gyrus, adult neurogenesis, and pattern separation. Neuron. 2011;70(4):589–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Sahay A, Wilson DA, Hen R. Pattern separation: a common function for new neurons in hippocampus and olfactory bulb. Neuron. 2011;70(4):582–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Levenson JM, O'Riordan KJ, Brown KD, Trinh MA, Molfese DL, Sweatt JD. Regulation of histone acetylation during memory formation in the hippocampus. J Biol Chem. 2004;279(39):40545–59.

    Article  CAS  PubMed  Google Scholar 

  110. Bading H. Transcription-dependent neuronal plasticity the nuclear calcium hypothesis. Eur J Biochem. 2000;267(17):5280–3.

    Article  CAS  PubMed  Google Scholar 

  111. West AE, Chen WG, Dalva MB, Dolmetsch RE, Kornhauser JM, Shaywitz AJ, Takasu MA, Tao X, Greenberg ME. Calcium regulation of neuronal gene expression. Proc Natl Acad Sci U S A. 2001;98(20):11024–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Hardingham GE, Chawla S, Johnson CM, Bading H. Distinct functions of nuclear and cytoplasmic calcium in the control of gene expression. Nature. 1997;385(6613):260–5.

    Article  CAS  PubMed  Google Scholar 

  113. Deisseroth K, Heist EK, Tsien RW. Translocation of calmodulin to the nucleus supports CREB phosphorylation in hippocampal neurons. Nature. 1998;392(6672):198–202.

    Article  CAS  PubMed  Google Scholar 

  114. Hardingham GE, Arnold FJ, Bading H. Nuclear calcium signaling controls CREB-mediated gene expression triggered by synaptic activity. Nat Neurosci. 2001;4(3):261–7.

    Article  CAS  PubMed  Google Scholar 

  115. Chetkovich DM, Gray R, Johnston D, Sweatt JD. N-methyl-D-aspartate receptor activation increases cAMP levels and voltage-gated Ca2+ channel activity in area CA1 of hippocampus. Proc Natl Acad Sci U S A. 1991;88(15):6467–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Dolmetsch RE, Pajvani U, Fife K, Spotts JM, Greenberg ME. Signaling to the nucleus by an L-type calcium channel-calmodulin complex through the MAP kinase pathway. Science. 2001;294(5541):333–9.

    Article  CAS  PubMed  Google Scholar 

  117. Limback-Stokin K, Korzus E, Nagaoka-Yasuda R, Mayford M. Nuclear calcium/calmodulin regulates memory consolidation. J Neurosci. 2004;24(48):10858–67.

    Article  PubMed  CAS  Google Scholar 

  118. Chawla S, Hardingham GE, Quinn DR, Bading H. CBP: a signal-regulated transcriptional coactivator controlled by nuclear calcium and CaM kinase IV. Science. 1998;281(5382):1505–9.

    Article  CAS  PubMed  Google Scholar 

  119. O'Carroll CM, Morris RG. Heterosynaptic co-activation of glutamatergic and dopaminergic afferents is required to induce persistent long-term potentiation. Neuropharmacology. 2004;47(3):324–32.

    Article  PubMed  CAS  Google Scholar 

  120. Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature. 2004;429(6990):457–63.

    Article  CAS  PubMed  Google Scholar 

  121. Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ. Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci. 2006;9(4):519–25.

    Article  CAS  PubMed  Google Scholar 

  122. Frey U, Morris RG. Synaptic tagging and long-term potentiation [see comments]. Nature. 1997;385(6616):533–6.

    Article  CAS  PubMed  Google Scholar 

  123. Cosgrove MS, Wolberger C. How does the histone code work? Biochem Cell Biol. 2005;83(4):468–76.

    Article  CAS  PubMed  Google Scholar 

  124. Luger K. Dynamic nucleosomes. Chromosome Res. 2006;14(1):5–16.

    Article  CAS  PubMed  Google Scholar 

  125. Day JJ, Sweatt JD. Epigenetic treatments for cognitive impairments. Neuropsychopharmacology. 2012;37(1):247–60.

    Article  CAS  PubMed  Google Scholar 

  126. Lopez-Atalaya JP, Gervasini C, Mottadelli F, Spena S, Piccione M, Scarano G, Selicorni A, Barco A, Larizza L. Histone acetylation deficits in lymphoblastoid cell lines from patients with Rubinstein-Taybi syndrome. J Med Genet. 2012;49(1):66–74.

    Article  CAS  PubMed  Google Scholar 

  127. Bredy TW, Barad M. The histone deacetylase inhibitor valproic acid enhances acquisition, extinction, and reconsolidation of conditioned fear. Learn Mem. 2008;15(1):39–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Roozendaal B, Hernandez A, Cabrera SM, Hagewoud R, Malvaez M, Stefanko DP, Haettig J, Wood MA. Membrane-associated glucocorticoid activity is necessary for modulation of long-term memory via chromatin modification. J Neurosci. 2010;30(14):5037–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. McQuown SC, Barrett RM, Matheos DP, Post RJ, Rogge GA, Alenghat T, Mullican SE, Jones S, Rusche JR, Lazar MA, Wood MA. HDAC3 is a critical negative regulator of long-term memory formation. J Neurosci. 2011;31(2):764–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Berdasco M, Esteller M. Genetic syndromes caused by mutations in epigenetic genes. Hum Genet. 2013;132(4):359–83.

    Article  CAS  PubMed  Google Scholar 

  131. Duraisingh MT, Horn D. Epigenetic regulation of virulence gene expression in parasitic protozoa. Cell Host Microbe. 2016;19(5):629–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Abel T, Zukin RS. Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders. Curr Opin Pharmacol. 2008;8(1):57–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Graff J, Mansuy IM. Epigenetic dysregulation in cognitive disorders. Eur J Neurosci. 2009;30(1):1–8.

    Article  PubMed  Google Scholar 

  134. Rudenko A, Tsai LH. Epigenetic modifications in the nervous system and their impact upon cognitive impairments. Neuropharmacology. 2014;80:70–82.

    Article  CAS  PubMed  Google Scholar 

  135. Schorry EK, Keddache M, Lanphear N, Rubinstein JH, Srodulski S, Fletcher D, Blough-Pfau RI, Grabowski GA. Genotype-phenotype correlations in Rubinstein-Taybi syndrome. Am J Med Genet A. 2008;146A(19):2512–9.

    Article  CAS  PubMed  Google Scholar 

  136. Rusconi D, Negri G, Colapietro P, Picinelli C, Milani D, Spena S, Magnani C, Silengo MC, Sorasio L, Curtisova V, Cavaliere ML, Prontera P, Stangoni G, Ferrero GB, Biamino E, Fischetto R, Piccione M, Gasparini P, Salviati L, Selicorni A, Finelli P, Larizza L, Gervasini C. Characterization of 14 novel deletions underlying Rubinstein-Taybi syndrome: an update of the CREBBP deletion repertoire. Hum Genet. 2015;134(6):613–26.

    Article  CAS  PubMed  Google Scholar 

  137. Wincent J, Luthman A, van Belzen M, van der Lans C, Albert J, Nordgren A, Anderlid BM. CREBBP and EP300 mutational spectrum and clinical presentations in a cohort of Swedish patients with Rubinstein-Taybi syndrome. Mol Genet Genomic Med. 2016;4(1):39–45.

    Article  CAS  PubMed  Google Scholar 

  138. Shanmugam MK, Sethi G. Role of epigenetics in inflammation-associated diseases. Subcell Biochem. 2013;61:627–57.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychology and Neuroscience Program, University Of California Riverside, 900 University Ave, Riverside, CA, 92521, USA

    Edward Korzus Ph.D.

Authors
  1. Edward Korzus Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Edward Korzus Ph.D. .

Editor information

Editors and Affiliations

  1. Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), CATALONIA, Spain

    Raul Delgado-Morales

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Korzus, E. (2017). Rubinstein-Taybi Syndrome and Epigenetic Alterations. In: Delgado-Morales, R. (eds) Neuroepigenomics in Aging and Disease. Advances in Experimental Medicine and Biology(), vol 978. Springer, Cham. https://doi.org/10.1007/978-3-319-53889-1_3

Download citation

Publish with us

Policies and ethics

Search

Navigation