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Neural Plasticity Volume 2019 ,2019-07-14
Writers and Readers of DNA Methylation/Hydroxymethylation in Physiological Aging and Its Impact on Cognitive Function
Review Article
Rodrigo F. Torres 1 , 2 Ricardo Kouro 1 , 3 Bredford Kerr 1 , 4
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DOI:10.1155/2019/5982625
Received 2019-02-22, accepted for publication 2019-05-26, Published 2019-05-26
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摘要

The chromatin landscape has acquired deep attention from several fields ranging from cell biology to neurological and psychiatric diseases. The role that DNA modifications have on gene expression regulation has become apparent in several physiological processes, and numerous efforts have been performed to establish a relationship between DNA modifications and physiological conditions, such as cognitive performance and aging. DNA modifications are incorporated by specific sets of enzymes—the writers—and the modified DNA-interacting partners—the readers—are ultimately responsible for maintaining a functional epigenetic landscape. Therefore, understanding how these epigenetic mediators—writers and readers—are modulated in physiological aging will contribute to unraveling how aging-associated neuronal disturbances arise and contribute to the cognitive decline associated with this period of life. In this review, we focused on DNA modifications, writers and readers, highlighting that despite some methodological disparities, the evidence suggests a critical role for epigenetic mediators in the aging-associated neuronal dysfunction.

授权许可

Copyright © 2019 Rodrigo F. Torres et al. 2019
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

通讯作者

1. Rodrigo F. Torres.Centro de Estudios Científicos, Valdivia 5110466, Chile, cecs.cl;Fundación Cultura Científica, Valdivia 5112119, Chile.rtorres@cecs.cl
2. Bredford Kerr.Centro de Estudios Científicos, Valdivia 5110466, Chile, cecs.cl;Centro de Biología Celular y Biomedicina-CEBICEM, Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago 7510157, Chile, uss.cl.bredford.kerr@uss.cl

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Rodrigo F. Torres,Ricardo Kouro,Bredford Kerr. Writers and Readers of DNA Methylation/Hydroxymethylation in Physiological Aging and Its Impact on Cognitive Function. Neural Plasticity ,Vol.2019(2019)

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[1] Z. Zhou, E. J. Hong, S. Cohen, W. N. Zhao. et al.(2006). Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation. Neuron.52(2):255-269. DOI: 10.1016/j.neuron.2015.03.033.
[2] D. Tropea, N. Mortimer, S. Bellini, I. Molinos. et al.(2016). Expression of nuclear methyl-CpG binding protein 2 (Mecp2) is dependent on neuronal stimulation and application of insulin-like growth factor 1. Neuroscience Letters.621:111-116. DOI: 10.1016/j.neuron.2015.03.033.
[3] M. Scali, L. Baroncelli, M. C. Cenni, A. Sale. et al.(2012). A rich environmental experience reactivates visual cortex plasticity in aged rats. Experimental Gerontology.47(4):337-341. DOI: 10.1016/j.neuron.2015.03.033.
[4] J. L. Abel, E. F. Rissman. (2013). Running-induced epigenetic and gene expression changes in the adolescent brain. International Journal of Developmental Neuroscience.31(6):382-390. DOI: 10.1016/j.neuron.2015.03.033.
[5] L. R. Stein, K. A. O’Dell, M. Funatsu, C. F. Zorumski. et al.(2016). Short-term environmental enrichment enhances synaptic plasticity in hippocampal slices from aged rats. Neuroscience.329:294-305. DOI: 10.1016/j.neuron.2015.03.033.
[6] R. E. Amir, I. B. Van den Veyver, M. Wan, C. Q. Tran. et al.(1999). Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nature Genetics.23(2):185-188. DOI: 10.1016/j.neuron.2015.03.033.
[7] B. Buchthal, D. Lau, U. Weiss, J.-M. Weislogel. et al.(2012). Nuclear calcium signaling controls methyl-CpG-binding protein 2 (MeCP2) phosphorylation on serine 421 following synaptic activity. Journal of Biological Chemistry.287(37):30967-30974. DOI: 10.1016/j.neuron.2015.03.033.
[8] A. M. Stranahan, K. Lee, K. G. Becker, Y. Zhang. et al.(2010). Hippocampal gene expression patterns underlying the enhancement of memory by running in aged mice. Neurobiology of Aging.31(11):1937-1949. DOI: 10.1016/j.neuron.2015.03.033.
[9] P. A. Jones, D. Takai. (2001). The role of DNA methylation in mammalian epigenetics. Science.293(5532):1068-1070. DOI: 10.1016/j.neuron.2015.03.033.
[10] X. Zou, W. Ma, I. A. Solov'yov, C. Chipot. et al.(2012). Recognition of methylated DNA through methyl-CpG binding domain proteins. Nucleic Acids Research.40(6):2747-2758. DOI: 10.1016/j.neuron.2015.03.033.
[11] Y. Li, L. Liu, T. O. Tollefsbol. (2010). Glucose restriction can extend normal cell lifespan and impair precancerous cell growth through epigenetic control of hTERT and p16 expression. The FASEB Journal.24(5):1442-1453. DOI: 10.1016/j.neuron.2015.03.033.
[12] D. Glass, A. Viñuela, M. N. Davies, A. Ramasamy. et al.(2013). Gene expression changes with age in skin, adipose tissue, blood and brain. Genome Biology.14(7, article R75). DOI: 10.1016/j.neuron.2015.03.033.
[13] F. Telese, Q. Ma, P. M. Perez, D. Notani. et al.(2015). LRP8-Reelin-regulated neuronal enhancer signature underlying learning and memory formation. Neuron.86(3):696-710. DOI: 10.1016/j.neuron.2015.03.033.
[14] S. A. S. Langie, K. M. Cameron, G. Ficz, D. Oxley. et al.(2017). The ageing brain: effects on DNA repair and DNA methylation in mice. Genes.8(2):75. DOI: 10.1016/j.neuron.2015.03.033.
[15] A. L. Collins, J. M. Levenson, A. P. Vilaythong, R. Richman. et al.(2004). Mild overexpression of MeCP2 causes a progressive neurological disorder in mice. Human Molecular Genetics.13(21):2679-2689. DOI: 10.1016/j.neuron.2015.03.033.
[16] B. H. Ramsahoye, D. Biniszkiewicz, F. Lyko, V. Clark. et al.(2000). Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a. Proceedings of the National Academy of Sciences of the United States of America.97(10):5237-5242. DOI: 10.1016/j.neuron.2015.03.033.
[17] C. Bas-Orth, Y.-W. Tan, D. Lau, H. Bading. et al.(2017). Synaptic activity drives a genomic program that promotes a neuronal Warburg effect. Journal of Biological Chemistry.292(13):5183-5194. DOI: 10.1016/j.neuron.2015.03.033.
[18] R. C. Samaco, R. P. Nagarajan, D. Braunschweig, J. M. LaSalle. et al.(2004). Multiple pathways regulate MeCP2 expression in normal brain development and exhibit defects in autism-spectrum disorders. Human Molecular Genetics.13(6):629-639. DOI: 10.1016/j.neuron.2015.03.033.
[19] M. Fasolino, S. Liu, Y. Wang, Z. Zhou. et al.(2017). Distinct cellular and molecular environments support aging-related DNA methylation changes in the substantia nigra. Epigenomics.9(1):21-31. DOI: 10.1016/j.neuron.2015.03.033.
[20] H. Stroud, S. C. Su, S. Hrvatin, A. W. Greben. et al.(2017). Early-life gene expression in neurons modulates lasting epigenetic states. Cell.171(5):1151-1164.e16. DOI: 10.1016/j.neuron.2015.03.033.
[21] J. Tao, K. Hu, Q. Chang, H. Wu. et al.(2009). Phosphorylation of MeCP2 at serine 80 regulates its chromatin association and neurological function. Proceedings of the National Academy of Sciences of the United States of America.106(12):4882-4887. DOI: 10.1016/j.neuron.2015.03.033.
[22] J. U. Guo, D. K. Ma, H. Mo, M. P. Ball. et al.(2011). Neuronal activity modifies the DNA methylation landscape in the adult brain. Nature Neuroscience.14(10):1345-1351. DOI: 10.1016/j.neuron.2015.03.033.
[23] S. Maegawa, Y. Lu, T. Tahara, J. T. Lee. et al.(2017). Caloric restriction delays age-related methylation drift. Nature Communications.8(1):539. DOI: 10.1016/j.neuron.2015.03.033.
[24] H. Chen, S. Dzitoyeva, H. Manev. (2012). Effect of aging on 5-hydroxymethylcytosine in the mouse hippocampus. Restorative Neurology and Neuroscience.30(3):237-245. DOI: 10.1016/j.neuron.2015.03.033.
[25] D. Balmer, J. Goldstine, Y. M. Rao, J. M. LaSalle. et al.(2003). Elevated methyl-CpG-binding protein 2 expression is acquired during postnatal human brain development and is correlated with alternative polyadenylation. Journal of Molecular Medicine.81(1):61-68. DOI: 10.1016/j.neuron.2015.03.033.
[26] P. Obiang, E. Maubert, I. Bardou, O. Nicole. et al.(2011). Enriched housing reverses age-associated impairment of cognitive functions and tPA-dependent maturation of BDNF. Neurobiology of Learning and Memory.96(2):121-129. DOI: 10.1016/j.neuron.2015.03.033.
[27] Y. Asaka, D. G. M. Jugloff, L. Zhang, J. H. Eubanks. et al.(2006). Hippocampal synaptic plasticity is impaired in the Mecp2-null mouse model of Rett syndrome. Neurobiology of Disease.21(1):217-227. DOI: 10.1016/j.neuron.2015.03.033.
[28] G. P. Cortese, A. Olin, K. O’Riordan, R. Hullinger. et al.(2018). Environmental enrichment improves hippocampal function in aged rats by enhancing learning and memory, LTP, and mGluR5-Homer1c activity. Neurobiology of Aging.63:1-11. DOI: 10.1016/j.neuron.2015.03.033.
[29] P. R. Patrylo, A. Williamson. (2007). The effects of aging on dentate circuitry and function. Progress in Brain Research.163:679-696. DOI: 10.1016/j.neuron.2015.03.033.
[30] L. Wang, M. Cao, T. Pu, H. Huang. et al.(2018). Enriched physical environment attenuates spatial and social memory impairments of aged socially isolated mice. The International Journal of Neuropsychopharmacology.21(12):1114-1127. DOI: 10.1016/j.neuron.2015.03.033.
[31] G. J. Pelka, C. M. Watson, T. Radziewic, M. Hayward. et al.(2006). deficiency is associated with learning and cognitive deficits and altered gene activity in the hippocampal region of mice. Brain.129(4):887-898. DOI: 10.1016/j.neuron.2015.03.033.
[32] K. L. Roberts, H. A. Allen. (2016). Perception and cognition in the ageing brain: a brief review of the short- and long-term links between perceptual and cognitive decline. Frontiers in Aging Neuroscience.8. DOI: 10.1016/j.neuron.2015.03.033.
[33] Z. A. Monge, D. J. Madden. (2016). Linking cognitive and visual perceptual decline in healthy aging: the information degradation hypothesis. Neuroscience and Biobehavioral Reviews.69:166-173. DOI: 10.1016/j.neuron.2015.03.033.
[34] A. Free, R. I. D. Wakefield, B. O. Smith, D. T. F. Dryden. et al.(2001). DNA recognition by the methyl-CpG binding domain of MeCP2. Journal of Biological Chemistry.276(5):3353-3360. DOI: 10.1016/j.neuron.2015.03.033.
[35] P. Moretti, J. M. Levenson, F. Battaglia, R. Atkinson. et al.(2006). Learning and memory and synaptic plasticity are impaired in a mouse model of Rett syndrome. The Journal of Neuroscience.26(1):319-327. DOI: 10.1016/j.neuron.2015.03.033.
[36] H. Cheval, J. Guy, C. Merusi, D. De Sousa. et al.(2012). Postnatal inactivation reveals enhanced requirement for MeCP2 at distinct age windows. Human Molecular Genetics.21(17):3806-3814. DOI: 10.1016/j.neuron.2015.03.033.
[37] S. Luikenhuis, E. Giacometti, C. F. Beard, R. Jaenisch. et al.(2004). Expression of MeCP2 in postmitotic neurons rescues Rett syndrome in mice. Proceedings of the National Academy of Sciences of the United States of America.101(16):6033-6038. DOI: 10.1016/j.neuron.2015.03.033.
[38] G. Gontier, M. Iyer, J. M. Shea, G. Bieri. et al.(2018). Tet2 rescues age-related regenerative decline and enhances cognitive function in the adult mouse brain. Cell Reports.22(8):1974-1981. DOI: 10.1016/j.neuron.2015.03.033.
[39] T. H. Bestor. (2000). The DNA methyltransferases of mammals. Human Molecular Genetics.9(16):2395-2402. DOI: 10.1016/j.neuron.2015.03.033.
[40] P. Jessop, M. Toledo-Rodriguez. (2018). Hippocampal TET1 and TET2 expression and DNA hydroxymethylation are affected by physical exercise in aged mice. Frontiers in Cell and Developmental Biology.6:45. DOI: 10.1016/j.neuron.2015.03.033.
[41] H. B. Fraser, P. Khaitovich, J. B. Plotkin, S. Pääbo. et al.(2005). Aging and gene expression in the primate brain. PLoS Biology.3(9, article e274). DOI: 10.1016/j.neuron.2015.03.033.
[42] R. J. Klose, A. P. Bird. (2006). Genomic DNA methylation: the mark and its mediators. Trends in Biochemical Sciences.31(2):89-97. DOI: 10.1016/j.neuron.2015.03.033.
[43] K. Gulmez Karaca, D. V. C. Brito, B. Zeuch, A. M. M. Oliveira. et al.(2018). Adult hippocampal MeCP2 preserves the genomic responsiveness to learning required for long-term memory formation. Neurobiology of Learning and Memory.149:84-97. DOI: 10.1016/j.neuron.2015.03.033.
[44] L. Liu, T. van Groen, I. Kadish, Y. Li. et al.(2011). Insufficient DNA methylation affects healthy aging and promotes age-related health problems. Clinical Epigenetics.2(2):349-360. DOI: 10.1016/j.neuron.2015.03.033.
[45] E. Bellini, G. Pavesi, I. Barbiero, A. Bergo. et al.(2014). MeCP2 post-translational modifications: a mechanism to control its involvement in synaptic plasticity and homeostasis?. Frontiers in Cellular Neuroscience.8:236. DOI: 10.1016/j.neuron.2015.03.033.
[46] A. M. M. Oliveira, T. J. Hemstedt, H. Bading. (2012). Rescue of aging-associated decline in Dnmt3a2 expression restores cognitive abilities. Nature Neuroscience.15(8):1111-1113. DOI: 10.1016/j.neuron.2015.03.033.
[47] H. Leonhardt, A. W. Page, H.-U. Weier, T. H. Bestor. et al.(1992). A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell.71(5):865-873. DOI: 10.1016/j.neuron.2015.03.033.
[48] S. E. Kee, X. Mou, H. Y. Zoghbi, D. Ji. et al.(2018). Impaired spatial memory codes in a mouse model of Rett syndrome. eLife.7. DOI: 10.1016/j.neuron.2015.03.033.
[49] C. S. Casas-Delucchi, A. Becker, J. J. Bolius, M. C. Cardoso. et al.(2012). Targeted manipulation of heterochromatin rescues MeCP2 Rett mutants and re-establishes higher order chromatin organization. Nucleic Acids Research.40(22, article e176). DOI: 10.1016/j.neuron.2015.03.033.
[50] R. F. Torres, C. Hidalgo, B. Kerr. (2017). Mecp2 mediates experience-dependent transcriptional upregulation of ryanodine receptor type-3. Frontiers in Molecular Neuroscience.10:188. DOI: 10.1016/j.neuron.2015.03.033.
[51] R. Bijkerk, C. Trimpert, C. van Solingen, R. G. de Bruin. et al.(2018). MicroRNA-132 controls water homeostasis through regulating MECP2-mediated vasopressin synthesis. American Journal of Physiology-Renal Physiology.315(4):F1129-F1138. DOI: 10.1016/j.neuron.2015.03.033.
[52] L. Ianov, A. Riva, A. Kumar, T. C. Foster. et al.(2017). DNA methylation of synaptic genes in the prefrontal cortex is associated with aging and age-related cognitive impairment. Frontiers in Aging Neuroscience.9. DOI: 10.1016/j.neuron.2015.03.033.
[53] X. Nan, H.-H. Ng, C. A. Johnson, C. D. Laherty. et al.(1998). Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature.393(6683):386-389. DOI: 10.1016/j.neuron.2015.03.033.
[54] M. Chahrour, S. Y. Jung, C. Shaw, X. Zhou. et al.(2008). MeCP2, a key contributor to neurological disease, activates and represses transcription. Science.320(5880):1224-1229. DOI: 10.1016/j.neuron.2015.03.033.
[55] C. O. Olson, R. M. Zachariah, C. D. Ezeonwuka, V. R. B. Liyanage. et al.(2014). Brain region-specific expression of MeCP2 isoforms correlates with DNA methylation within Mecp2 regulatory elements. PLoS One.9(3, article e90645). DOI: 10.1016/j.neuron.2015.03.033.
[56] A. Becker, P. Zhang, L. Allmann, D. Meilinger. et al.(2016). Poly(ADP-ribosyl)ation of methyl CpG binding domain protein 2 regulates chromatin structure. Journal of Biological Chemistry.291(10):4873-4881. DOI: 10.1016/j.neuron.2015.03.033.
[57] M. Zampieri, F. Ciccarone, R. Calabrese, C. Franceschi. et al.(2015). Reconfiguration of DNA methylation in aging. Mechanisms of Ageing and Development.151:60-70. DOI: 10.1016/j.neuron.2015.03.033.
[58] Y. Alaghband, T. W. Bredy, M. A. Wood. (2016). The role of active DNA demethylation and Tet enzyme function in memory formation and cocaine action. Neuroscience Letters.625:40-46. DOI: 10.1016/j.neuron.2015.03.033.
[59] H. A. Irier, P. Jin. (2012). Dynamics of DNA methylation in aging and Alzheimer’s disease. DNA and Cell Biology.31:S-42-S-48. DOI: 10.1016/j.neuron.2015.03.033.
[60] Z. Tong, C. Han, M. Qiang, W. Wang. et al.(2015). Age-related formaldehyde interferes with DNA methyltransferase function, causing memory loss in Alzheimer’s disease. Neurobiology of Aging.36(1):100-110. DOI: 10.1016/j.neuron.2015.03.033.
[61] J.-P. Etchegaray, R. Mostoslavsky. (2016). Interplay between metabolism and epigenetics: a nuclear adaptation to environmental changes. Molecular Cell.62(5):695-711. DOI: 10.1016/j.neuron.2015.03.033.
[62] J. U. Guo, Y. Su, J. H. Shin, J. Shin. et al.(2014). Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain. Nature Neuroscience.17(2):215-222. DOI: 10.1016/j.neuron.2015.03.033.
[63] A. Rudenko, M. M. Dawlaty, J. Seo, A. W. Cheng. et al.(2013). Tet1 is critical for neuronal activity-regulated gene expression and memory extinction. Neuron.79(6):1109-1122. DOI: 10.1016/j.neuron.2015.03.033.
[64] H. Irier, R. C. Street, R. Dave, L. Lin. et al.(2014). Environmental enrichment modulates 5-hydroxymethylcytosine dynamics in hippocampus. Genomics.104(5):376-382. DOI: 10.1016/j.neuron.2015.03.033.
[65] S. Pal, J. K. Tyler. (2016). Epigenetics and aging. Science Advances.2(7, article e1600584). DOI: 10.1016/j.neuron.2015.03.033.
[66] J. Nithianantharajah, A. J. Hannan. (2006). Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nature Reviews Neuroscience.7(9):697-709. DOI: 10.1016/j.neuron.2015.03.033.
[67] S. Fusco, C. Ripoli, M. V. Podda, S. C. Ranieri. et al.(2012). A role for neuronal cAMP responsive-element binding (CREB)-1 in brain responses to calorie restriction. Proceedings of the National Academy of Sciences of the United States of America.109(2):621-626. DOI: 10.1016/j.neuron.2015.03.033.
[68] J. Fernandes, R. M. Arida, F. Gomez-Pinilla. (2017). Physical exercise as an epigenetic modulator of brain plasticity and cognition. Neuroscience and Biobehavioral Reviews.80:443-456. DOI: 10.1016/j.neuron.2015.03.033.
[69] E. J. Ryu, H. P. Harding, J. M. Angelastro, O. V. Vitolo. et al.(2002). Endoplasmic reticulum stress and the unfolded protein response in cellular models of Parkinson’s disease. The Journal of Neuroscience.22(24):10690-10698. DOI: 10.1016/j.neuron.2015.03.033.
[70] E. Korzus, M. G. Rosenfeld, M. Mayford. (2004). CBP histone acetyltransferase activity is a critical component of memory consolidation. Neuron.42(6):961-972. DOI: 10.1016/j.neuron.2015.03.033.
[71] A. Marco, T. Kisliouk, T. Tabachnik, A. Weller. et al.(2016). DNA CpG methylation (5-methylcytosine) and its derivative (5-hydroxymethylcytosine) alter histone posttranslational modifications at the Pomc promoter, affecting the impact of perinatal diet on leanness and obesity of the offspring. Diabetes.65(8):2258-2267. DOI: 10.1016/j.neuron.2015.03.033.
[72] M. Mellén, P. Ayata, S. Dewell, S. Kriaucionis. et al.(2012). MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system. Cell.151(7):1417-1430. DOI: 10.1016/j.neuron.2015.03.033.
[73] F. Ciccarone, S. Tagliatesta, P. Caiafa, M. Zampieri. et al.(2018). DNA methylation dynamics in aging: how far are we from understanding the mechanisms?. Mechanisms of Ageing and Development.174:3-17. DOI: 10.1016/j.neuron.2015.03.033.
[74] R. Halder, M. Hennion, R. O. Vidal, O. Shomroni. et al.(2016). DNA methylation changes in plasticity genes accompany the formation and maintenance of memory. Nature Neuroscience.19(1):102-110. DOI: 10.1016/j.neuron.2015.03.033.
[75] B. C. Christensen, E. A. Houseman, C. J. Marsit, S. Zheng. et al.(2009). Aging and environmental exposures Aater tissue-specific DNA methylation dependent upon CpG island context. PLOS Genetics.5(8, article e1000602). DOI: 10.1016/j.neuron.2015.03.033.
[76] J. Cortés-Mendoza, S. Díaz de León-Guerrero, G. Pedraza-Alva, L. Pérez-Martínez. et al.(2013). Shaping synaptic plasticity: the role of activity-mediated epigenetic regulation on gene transcription. International Journal of Developmental Neuroscience.31(6):359-369. DOI: 10.1016/j.neuron.2015.03.033.
[77] J. Yang, E. Ruchti, J.-M. Petit, P. Jourdain. et al.(2014). Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons. Proceedings of the National Academy of Sciences of the United States of America.111(33):12228-12233. DOI: 10.1016/j.neuron.2015.03.033.
[78] M. Jung, G. P. Pfeifer. (2015). Aging and DNA methylation. BMC Biology.13(1). DOI: 10.1016/j.neuron.2015.03.033.
[79] X. Wu, Y. Zhang. (2017). TET-mediated active DNA demethylation: mechanism, function and beyond. Nature Reviews Genetics.18(9):517-534. DOI: 10.1016/j.neuron.2015.03.033.
[80] E. Palomer, A. Martín-Segura, S. Baliyan, T. Ahmed. et al.(2016). Aging triggers a repressive chromatin state at Bdnf promoters in hippocampal neurons. Cell Reports.16(11):2889-2900. DOI: 10.1016/j.neuron.2015.03.033.
[81] S. Dzitoyeva, H. Chen, H. Manev. (2012). Effect of aging on 5-hydroxymethylcytosine in brain mitochondria. Neurobiology of Aging.33(12):2881-2891. DOI: 10.1016/j.neuron.2015.03.033.
[82] C. G. Duke, A. J. Kennedy, C. F. Gavin, J. J. Day. et al.(2017). Experience-dependent epigenomic reorganization in the hippocampus. Learning & Memory.24(7):278-288. DOI: 10.1016/j.neuron.2015.03.033.
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