Epigenetics of Sleep and Chronobiology

  • Irfan A. Qureshi
  • Mark F. MehlerEmail author
Sleep (M Thorpy, M Billiard, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Sleep


The circadian clock choreographs fundamental biological rhythms. This system is comprised of the master circadian pacemaker in the suprachiasmatic nucleus and associated pacemakers in other tissues that coordinate complex physiological processes and behaviors, such as sleep, feeding, and metabolism. The molecular circuitry that underlies these clocks and orchestrates circadian gene expression has been the focus of intensive investigation, and it is becoming clear that epigenetic factors are highly integrated into these networks. In this review, we draw attention to the fundamental roles played by epigenetic mechanisms in transcriptional and post-transcriptional regulation within the circadian clock system. We also highlight how alterations in epigenetic factors and mechanisms are being linked with sleep-wake disorders. These observations provide important insights into the pathogenesis and potential treatment of these disorders and implicate epigenetic deregulation in the significant but poorly understood interconnections now emerging between circadian processes and neurodegeneration, metabolic diseases, cancer, and aging.


Circadian Chromatin DNA methylation Epigenetic Histone modification Long noncoding RNA MicroRNA Noncoding RNA RNA editing Sleep 


Compliance with Ethics Guidelines

Conflict of Interest

Irfan A. Qureshi declares that he has no conflict of interest. Mark F. Mehler is supported by grants from the National Institutes of Health (NS071571, HD071593, MH66290), as well as by the F.M. Kirby, Alpern Family, Harold and Isabel Feld and Roslyn and Leslie Goldstein Foundations.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Mehler MF. Epigenetic principles and mechanisms underlying nervous system functions in health and disease. Prog Neurobiol. 2008;86:305–41.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Qureshi IA, Mehler MF. Emerging roles of noncoding RNAs in brain evolution, development, plasticity and disease. Nat Rev Neurosci. 2012;13:528–41.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Portela A, Esteller M. Epigenetic modifications and human disease. Nat Biotechnol [Review]. 2010;28:1057–68.CrossRefGoogle Scholar
  4. 4.
    Qureshi IA, Mehler MF. Understanding neurological disease mechanisms in the era of epigenetics. JAMA Neurol. 2013;70:703–10.PubMedCrossRefGoogle Scholar
  5. 5.
    Qureshi IA, Mehler MF. Developing epigenetic diagnostics and therapeutics for brain disorders. Trends Mol Med. 2013;19(12):732–41.PubMedCrossRefGoogle Scholar
  6. 6.
    Qureshi IA, Mehler MF. Long noncoding RNAs: novel targets for nervous system disease diagnosis and therapy. Neurotherapeutics. 2013;10:632–46.PubMedCrossRefGoogle Scholar
  7. 7.
    Masri S, Sassone-Corsi P. The circadian clock: a framework linking metabolism, epigenetics and neuronal function. Nat Rev Neurosci. 2012;14:69–75.PubMedCrossRefGoogle Scholar
  8. 8.
    Albrecht U. Timing to perfection: the biology of central and peripheral circadian clocks. Neuron. 2012;74:246–60.PubMedCrossRefGoogle Scholar
  9. 9.
    Lim C, Allada R. Emerging roles for post-transcriptional regulation in circadian clocks. Nat Neurosci. 2013;16:1544–50.PubMedCrossRefGoogle Scholar
  10. 10.
    Mellen M, Ayata P, Dewell S, et al. MeCP2 Binds to 5hmC enriched within active genes and accessible chromatin in the nervous system. Cell. 2012;151:1417–30.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Jin SG, Wu X, Li AX, Pfeifer GP. Genomic mapping of 5-hydroxymethylcytosine in the human brain. Nucleic Acids Res. 2011;39:5015–24.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Bonsch D, Hothorn T, Krieglstein C, et al. Daily variations of homocysteine concentration may influence methylation of DNA in normal healthy individuals. Chronobiol Int. 2007;24:315–26.PubMedCrossRefGoogle Scholar
  13. 13.
    Li JZ, Bunney BG, Meng F, et al. Circadian patterns of gene expression in the human brain and disruption in major depressive disorder. Proc Natl Acad Sci U S A. 2013;110:9950–5.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Maekawa F, Shimba S, Takumi S, et al. Diurnal expression of Dnmt3b mRNA in mouse liver is regulated by feeding and hepatic clockwork. Epigenetics. 2012;7:1046–56.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Zhou Z, Hong EJ, Cohen S, et al. Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation. Neuron. 2006;52:255–69.PubMedCrossRefGoogle Scholar
  16. 16.
    Belden WJ, Lewis ZA, Selker EU, et al. CHD1 remodels chromatin and influences transient DNA methylation at the clock gene frequency. PLoS Genet. 2011;7:e1002166.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Ji Y, Qin Y, Shu H, Li X. Methylation analyses on promoters of mPer1, mPer2, and mCry1 during perinatal development. Biochem Biophys Res Commun. 2010;391:1742–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Zhang L, Lin QL, Lu L, et al. Tissue-specific modification of clock methylation in aging mice. Eur Rev Med Pharmacol Sci. 2013;17:1874–80.PubMedGoogle Scholar
  19. 19.
    Nakatome M, Orii M, Hamajima M, et al. Methylation analysis of circadian clock gene promoters in forensic autopsy specimens. Leg Med. 2011;13:205–9.CrossRefGoogle Scholar
  20. 20.
    Neumann O, Kesselmeier M, Geffers R, et al. Methylome analysis and integrative profiling of human HCCs identify novel protumorigenic factors. Hepatology. 2012;56:1817–27.PubMedCrossRefGoogle Scholar
  21. 21.
    Hanoun M, Eisele L, Suzuki M, et al. Epigenetic silencing of the circadian clock gene CRY1 is associated with an indolent clinical course in chronic lymphocytic leukemia. PLoS One. 2012;7:e34347.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Hoffman AE, Zheng T, Yi CH, et al. The core circadian gene Cryptochrome 2 influences breast cancer risk, possibly by mediating hormone signaling. Cancer Prev Res. 2010;3:539–48.CrossRefGoogle Scholar
  23. 23.
    Taniguchi H, Fernandez AF, Setien F, et al. Epigenetic inactivation of the circadian clock gene BMAL1 in hematologic malignancies. Cancer Res. 2009;69:8447–54.PubMedCrossRefGoogle Scholar
  24. 24.
    Milagro FI, Gomez-Abellan P, Campion J, et al. CLOCK, PER2 and BMAL1 DNA methylation: association with obesity and metabolic syndrome characteristics and monounsaturated fat intake. Chronobiol Int. 2012;29:1180–94.PubMedCrossRefGoogle Scholar
  25. 25.
    Wither RG, Colic S, Wu C, et al. Daily rhythmic behaviors and thermoregulatory patterns are disrupted in adult female MeCP2-deficient mice. PLoS One. 2012;7:e35396.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.••
    Nanduri J, Makarenko V, Reddy VD, et al. Epigenetic regulation of hypoxic sensing disrupts cardiorespiratory homeostasis. Proc Natl Acad Sci U S A. 2012;109:2515–20. This paper demonstrated that DNA methylation plays a role in the neonatal programming of hypoxic sensitivity and subsequent autonomic deregulation during adulthood.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Young D, Nagarajan L, de Klerk N, et al. Sleep problems in Rett syndrome. Brain Dev. 2007;29:609–16.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Winkelmann J, Lin L, Schormair B, et al. Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy. Hum Mol Genet. 2012;21:2205–10.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Pedroso JL, Povoas Barsottini OG, Lin L, et al. A novel de novo exon 21 DNMT1 mutation causes cerebellar ataxia, deafness, and narcolepsy in a Brazilian patient. Sleep. 2013;36:1257–9, 59A.PubMedCentralPubMedGoogle Scholar
  30. 30.
    Syeda F, Fagan RL, Wean M, et al. The replication focus targeting sequence (RFTS) domain is a DNA-competitive inhibitor of Dnmt1. J Biol Chem. 2011;286:15344–51.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Bollati V, Baccarelli A, Sartori S, et al. Epigenetic effects of shiftwork on blood DNA methylation. Chronobiol Int. 2010;27:1093–104.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Zhu Y, Stevens RG, Hoffman AE, et al. Epigenetic impact of long-term shiftwork: pilot evidence from circadian genes and whole-genome methylation analysis. Chronobiol Int. 2011;28:852–61.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Shi F, Chen X, Fu A, et al. Aberrant DNA methylation of miR-219 promoter in long-term night shiftworkers. Environ Mol Mutagen. 2013;54:406–13.PubMedCrossRefGoogle Scholar
  34. 34.
    Jacobs DI, Hansen J, Fu A, et al. Methylation alterations at imprinted genes detected among long-term shiftworkers. Environ Mol Mutagen. 2013;54:141–6.PubMedCrossRefGoogle Scholar
  35. 35.
    Kim J, Bhattacharjee R, Khalyfa A, et al. DNA methylation in inflammatory genes among children with obstructive sleep apnea. Am J Respir Crit Care Med. 2012;185:330–8.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Rotter A, Asemann R, Decker A, et al. Orexin expression and promoter-methylation in peripheral blood of patients suffering from major depressive disorder. J Affect Disord. 2011;131:186–92.PubMedCrossRefGoogle Scholar
  37. 37.
    Lin Q, Ding H, Zheng Z, et al. Promoter methylation analysis of seven clock genes in Parkinson's disease. Neurosci Lett. 2012;507:147–50.PubMedCrossRefGoogle Scholar
  38. 38.
    Liu HC, Hu CJ, Tang YC, Chang JG. A pilot study for circadian gene disturbance in dementia patients. Neurosci Lett. 2008;435:229–33.PubMedCrossRefGoogle Scholar
  39. 39.••
    Hirayama J, Sahar S, Grimaldi B, et al. CLOCK-mediated acetylation of BMAL1 controls circadian function. Nature. 2007;450:1086–90. This study revealed that the CLOCK protein serves as a histone acetyltransferase enzyme and that this activity plays a role in mediating circadian gene expression.PubMedCrossRefGoogle Scholar
  40. 40.
    Etchegaray JP, Lee C, Wade PA, Reppert SM. Rhythmic histone acetylation underlies transcription in the mammalian circadian clock. Nature. 2003;421:177–82.PubMedCrossRefGoogle Scholar
  41. 41.•
    Valekunja UK, Edgar RS, Oklejewicz M, et al. Histone methyltransferase MLL3 contributes to genome-scale circadian transcription. Proc Natl Acad Sci U S A. 2013;110:1554–9. This analysis showed that the expression and function of the mixed lineage leukemia 3, a histone-modifying enzyme, is controlled by the circadian clock and is involved in regulating rhythmic gene expression on a genome-wide scale.PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Katada S, Sassone-Corsi P. The histone methyltransferase MLL1 permits the oscillation of circadian gene expression. Nat Struct Mol Biol. 2010;17:1414–21.PubMedCrossRefGoogle Scholar
  43. 43.
    DiTacchio L, Le HD, Vollmers C, et al. Histone lysine demethylase JARID1a activates CLOCK-BMAL1 and influences the circadian clock. Science. 2011;333:1881–5.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Cha J, Zhou M, Liu Y. CATP is a critical component of the Neurospora circadian clock by regulating the nucleosome occupancy rhythm at the frequency locus. EMBO Rep. 2013;14:923–30.PubMedCrossRefGoogle Scholar
  45. 45.•
    Nakahata Y, Kaluzova M, Grimaldi B, et al. The NAD + -dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell. 2008;134:329–40. This paper reported that NAD + -dependent sirtuin 1 is a histone deacetylase, which is involved in regulating circadian gene expression, and whose enzymatic activity is, both, dependent on cellular metabolic state and subject to circadian regulation.PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Asher G, Gatfield D, Stratmann M, et al. SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell. 2008;134:317–28.PubMedCrossRefGoogle Scholar
  47. 47.
    Nakahata Y, Sahar S, Astarita G, et al. Circadian control of the NA + salvage pathway by CLOCK-SIRT1. Science. 2009;324:654–7.PubMedCrossRefGoogle Scholar
  48. 48.
    Ramsey KM, Yoshino J, Brace CS, et al. Circadian clock feedback cycle through NAMPT-mediated NAD + biosynthesis. Science. 2009;324:651–4.PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Singh N, Lorbeck MT, Zervos A, et al. The histone acetyltransferase Elp3 plays in active role in the control of synaptic bouton expansion and sleep in Drosophila. J Neurochem. 2010;115:493–504.PubMedCrossRefGoogle Scholar
  50. 50.
    Pirooznia SK, Chiu K, Chan MT, et al. Epigenetic regulation of axonal growth of Drosophila pacemaker cells by histone acetyltransferase tip60 controls sleep. Genetics. 2012;192:1327–45.PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Gottlieb DJ, O'Connor GT, Wilk JB. Genome-wide association of sleep and circadian phenotypes. BMC Med Genet. 2007;8 Suppl 1:S9.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Kleefstra T, Smidt M, Banning MJ, et al. Disruption of the gene Euchromatin Histone Methyl Transferase1 (Eu-HMTase1) is associated with the 9q34 subtelomeric deletion syndrome. J Med Genet. 2005;42:299–306.PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Kleefstra T, Brunner HG, Amiel J, et al. Loss-of-function mutations in euchromatin histone methyl transferase 1 (EHMT1) cause the 9q34 subtelomeric deletion syndrome. Am J Hum Genet. 2006;79:370–7.PubMedCentralPubMedCrossRefGoogle Scholar
  54. 54.
    Verhoeven WM, Kleefstra T, Egger JI. Behavioral phenotype in the 9q subtelomeric deletion syndrome: a report about two adult patients. Am J Med Genet B Neuropsychiatr Genet. 2010;153B:536–41.PubMedGoogle Scholar
  55. 55.
    Williams SR, Aldred MA, Der Kaloustian VM, et al. Haploinsufficiency of HDAC4 causes brachydactyly mental retardation syndrome, with brachydactyly type E, developmental delays, and behavioral problems. Am J Hum Genet. 2010;87:219–28.PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Villavicencio-Lorini P, Klopocki E, Trimborn M, et al. Phenotypic variant of Brachydactyly-mental retardation syndrome in a family with an inherited interstitial 2q37.3 microdeletion including HDAC4. Eur J Hum Genet. 2013;21:743–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Williams SR, Zies D, Mullegama SV, et al. Smith-Magenis syndrome results in disruption of CLOCK gene transcription and reveals an integral role for RAI1 in the maintenance of circadian rhythmicity. Am J Hum Genet. 2012;90:941–9.PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.•
    Deardorff MA, Bando M, Nakato R, et al. HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle. Nature. 2012;489:313–7. This investigation identified loss-of-function mutations in the histone deacetylase 8 gene that deregulate the cohesin complex and are responsible for causing Cornelia de Lange syndrome.PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Rajan R, Benke JR, Kline AD, et al. Insomnia in Cornelia de Lange syndrome. Int J Pediatr Otorhinolaryngol. 2012;76:972–5.PubMedCrossRefGoogle Scholar
  60. 60.
    Stavinoha RC, Kline AD, Levy HP, et al. Characterization of sleep disturbance in Cornelia de Lange Syndrome. Int J Pediatr Otorhinolaryngol. 2011;75:215–8.PubMedCrossRefGoogle Scholar
  61. 61.
    Askarian-Amiri ME, Crawford J, French JD, et al. SNORD-host RNA Zfas1 is a regulator of mammary development and a potential marker for breast cancer. RNA. 2011;17:878–91.PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Clokie SJ, Lau P, Kim HH, et al. MicroRNAs in the pineal gland: miR-483 regulates melatonin synthesis by targeting arylalkylamine N-acetyltransferase. J Biol Chem. 2012;287:25312–24.PubMedCentralPubMedCrossRefGoogle Scholar
  63. 63.
    Xu S, Witmer PD, Lumayag S, et al. MicroRNA (miRNA) transcriptome of mouse retina and identification of a sensory organ-specific miRNA cluster. J Biol Chem. 2007;282:25053–66.PubMedCrossRefGoogle Scholar
  64. 64.
    Sire C, Moreno AB, Garcia-Chapa M, et al. Diurnal oscillation in the accumulation of Arabidopsis microRNAs, miR167, miR168, miR171 and miR398. FEBS Lett. 2009;583:1039–44.PubMedCrossRefGoogle Scholar
  65. 65.
    Yang M, Lee JE, Padgett RW, Edery I. Circadian regulation of a limited set of conserved microRNAs in Drosophila. BMC Genomics. 2008;9:83.PubMedCentralPubMedCrossRefGoogle Scholar
  66. 66.
    Vodala S, Pescatore S, Rodriguez J, et al. The oscillating miRNA 959-964 cluster impacts Drosophila feeding time and other circadian outputs. Cell Metab. 2012;16:601–12.PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Davis CJ, Bohnet SG, Meyerson JM, Krueger JM. Sleep. loss changes microRNA levels in the brain: a possible mechanism for state-dependent translational regulation. Neurosci Lett. 2007;422:68–73.PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Davis CJ, Clinton JM, Krueger JM. MicroRNA 138, let-7b, and 125a inhibitors differentially alter sleep and EEG delta-wave activity in rats. J Appl Physiol. 2012;113:1756–62.PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.••
    Cheng HY, Papp JW, Varlamova O, et al. microRNA modulation of circadian-clock period and entrainment. Neuron. 2007;54:813–29. This paper provided the first, robust mechanistic evidence that environmentally responsive microRNA activity is involved in the circadian clock within the suprachiasmatic nucleus.PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    Gatfield D, Le Martelot G, Vejnar CE, et al. Integration of microRNA miR-122 in hepatic circadian gene expression. Genes Dev. 2009;23:1313–26.PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.
    Na YJ, Sung JH, Lee SC, et al. Comprehensive analysis of microRNA-mRNA co-expression in circadian rhythm. Exp Mol Med. 2009;41:638–47.PubMedCentralPubMedCrossRefGoogle Scholar
  72. 72.
    Kadener S, Menet JS, Sugino K, et al. A role for microRNAs in the Drosophila circadian clock. Genes Dev. 2009;23:2179–91.PubMedCentralPubMedCrossRefGoogle Scholar
  73. 73.
    Nagel R, Clijsters L, Agami R. The miRNA-192/194 cluster regulates the Period gene family and the circadian clock. FEBS J. 2009;276:5447–55.PubMedCrossRefGoogle Scholar
  74. 74.
    Shende VR, Goldrick MM, Ramani S, Earnest DJ. Expression and rhythmic modulation of circulating microRNAs targeting the clock gene Bmal1 in mice. PLoS One. 2011;6:e22586.PubMedCentralPubMedCrossRefGoogle Scholar
  75. 75.
    Alvarez-Saavedra M, Antoun G, Yanagiya A, et al. miRNA-132 orchestrates chromatin remodeling and translational control of the circadian clock. Hum Mol Genet. 2011;20:731–51.PubMedCentralPubMedCrossRefGoogle Scholar
  76. 76.
    Zhang Y, Emery P. GW182 controls Drosophila circadian behavior and PDF-receptor signaling. Neuron. 2013;78:152–65.PubMedCrossRefGoogle Scholar
  77. 77.
    Lee KH, Kim SH, Lee HR, et al. MicroRNA-185 oscillation controls circadian amplitude of mouse Cryptochrome 1 via translational regulation. Mol Biol Cell. 2013;24:2248–55.PubMedCentralPubMedCrossRefGoogle Scholar
  78. 78.
    Chen R, D'Alessandro M, Lee C. miRNAs are required for generating a time delay critical for the circadian oscillator. Curr Biol. 2013;23:1959–68.PubMedCrossRefGoogle Scholar
  79. 79.•
    Hughes ME, Grant GR, Paquin C, et al. Deep sequencing the circadian and diurnal transcriptome of Drosophila brain. Genome Res. 2012;22:1266–81. This study performed RNA sequencing of Drosophila brain and identified hundreds of transcripts with circadian expression profiles, including many noncoding RNAs and those that were targets of RNA editing.PubMedCentralPubMedCrossRefGoogle Scholar
  80. 80.•
    Coon SL, Munson PJ, Cherukuri PF, et al. Circadian changes in long noncoding RNAs in the pineal gland. Proc Natl Acad Sci U S A. 2012;109:13319–24. This investigation of long noncoding RNA profiles in the rat pineal gland found diurnal expression patterns for 112 transcripts that were responsive to light exposure and regulated by norepinephrine signaling from the suprachiasmatic nucleus.PubMedCentralPubMedCrossRefGoogle Scholar
  81. 81.
    Menet JS, Rodriguez J, Abruzzi KC, Rosbash M. Nascent-Seq reveals novel features of mouse circadian transcriptional regulation. ELife. 2012;1:e00011.PubMedCentralPubMedCrossRefGoogle Scholar
  82. 82.
    Davis CJ, Clinton JM, Taishi P, et al. MicroRNA 132 alters sleep and varies with time in brain. J Appl Physiol. 2011;111:665–72.PubMedCentralPubMedCrossRefGoogle Scholar
  83. 83.
    Soshnev AA, Ishimoto H, McAllister BF, et al. A conserved long noncoding RNA affects sleep behavior in Drosophila. Genetics. 2011;189:455–68.PubMedCentralPubMedCrossRefGoogle Scholar
  84. 84.
    Saus E, Soria V, Escaramis G, et al. Genetic variants and abnormal processing of pre-miR-182, a circadian clock modulator, in major depression patients with late insomnia. Hum Mol Genet. 2010;19:4017–25.PubMedCrossRefGoogle Scholar
  85. 85.•
    Powell WT, Coulson RL, Crary FK, et al. A Prader-Willi locus lncRNA cloud modulates diurnal genes and energy expenditure. Hum Mol Genet. 2013;22:4318–28. This analysis of the 116HG long noncoding RNA encoded by the imprinted Prader-Willi locus suggested that this factor is involved in transcriptional regulation of key metabolic and clock genes, in postnatal neurons and during sleep, via the formation of a novel subnuclear domain.PubMedCentralPubMedCrossRefGoogle Scholar
  86. 86.
    Jepson JE, Savva YA, Yokose C, et al. Engineered alterations in RNA editing modulate complex behavior in Drosophila: regulatory diversity of adenosine deaminase acting on RNA (ADAR) targets. J Biol Chem. 2011;286:8325–37.PubMedCentralPubMedCrossRefGoogle Scholar
  87. 87.•
    Fustin JM, Doi M, Yamaguchi Y, et al. RNA-methylation-dependent RNA processing controls the speed of the circadian clock. Cell. 2013;155:793–806. This paper demonstrated that post-transcriptional RNA methylation is a novel component of the circadian clock responsible for targeting core clock transcripts and thereby regulating the length of the circadian period.PubMedCrossRefGoogle Scholar
  88. 88.
    Qureshi IA, Mehler MF. Towards a 'systems'-level understanding of the nervous system and its disorders. Trends Neurosci. 2013;36:674–84.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Roslyn and Leslie Goldstein Laboratory for Stem Cell Biology and Regenerative MedicineAlbert Einstein College of MedicineBronxUSA
  2. 2.Institute for Brain Disorders and Neural RegenerationAlbert Einstein College of MedicineBronxUSA
  3. 3.Department of NeurologyAlbert Einstein College of MedicineBronxUSA
  4. 4.Departments of NeuroscienceAlbert Einstein College of MedicineBronxUSA
  5. 5.Departments of Psychiatry and Behavioral SciencesAlbert Einstein College of MedicineBronxUSA
  6. 6.Rose F. Kennedy Center for Research on Intellectual and Developmental DisabilitiesAlbert Einstein College of MedicineBronxUSA
  7. 7.Ruth S. and David L. Gottesman Stem Cell InstituteAlbert Einstein College of MedicineBronxUSA
  8. 8.Center for EpigenomicsAlbert Einstein College of MedicineBronxUSA
  9. 9.Institute for Aging ResearchAlbert Einstein College of MedicineBronxUSA

Personalised recommendations