Quantification of cytosine modifications in the aged mouse brain.
5-formylcytosine: 5-fC
5-hydroxymethycytosine: 5-hmC
5-methylcytosine: 5-mC
aging
basal ganglia
Journal
Neuropsychopharmacology reports
ISSN: 2574-173X
Titre abrégé: Neuropsychopharmacol Rep
Pays: United States
ID NLM: 101719700
Informations de publication
Date de publication:
06 Dec 2023
06 Dec 2023
Historique:
revised:
18
10
2023
received:
24
08
2023
accepted:
25
10
2023
medline:
7
12
2023
pubmed:
7
12
2023
entrez:
7
12
2023
Statut:
aheadofprint
Résumé
Quantifying cytosine modifications in various brain regions provides important insights into the gene expression regulation and pathophysiology of neuropsychiatric disorders. In this study, we quantified 5-methylcytosine (5-mC), 5-hydroxymethylation (5-hmC), and 5-formylcytosine (5-fC) levels in five brain regions (the frontal lobe, cerebral cortical region without frontal lobe, hippocampus, basal ganglia, and the cerebellum) and the heart at three developmental periods (12, 48, and 101 weeks). We observed significant regional variations in cytosine modification. Notably, regional variations were generally maintained throughout development, suggesting that epigenetic regulation is unique to each brain region and remains relatively stable with age. The 5-mC and 5-hmC levels were positively correlated, although the extent of the correlations seemed to differ in different brain regions. On the contrary, 5-fC levels did not correlate with 5-mC or 5-hmC levels. Additionally, we observed an age-dependent decrease in 5-fC levels in the basal ganglia, suggesting a unique epigenetic regulation mechanism. Further high-resolution studies using animal models of neuropsychiatric disorders as well as postmortem brain evaluation are warranted.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Japan Agency for Medical Research and Development
ID : JP19dm0207074
Organisme : JSPS KAKENHI
ID : 18H05428
Organisme : JSPS KAKENHI
ID : 18H05430
Organisme : JSPS KAKENHI
ID : 18K15486
Organisme : JSPS KAKENHI
ID : 21K07548
Informations de copyright
© 2023 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Society of Neuropsychopharmacology.
Références
Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002;16(1):6-21.
Feinberg AP. Phenotypic plasticity and the epigenetics of human disease. Nature. 2007;447(7143):433-440.
Kular L, Kular S. Epigenetics applied to psychiatry: clinical opportunities and future challenges. Psychiatry Clin Neurosci. 2018;72(4):195-211.
Nishioka M, Bundo M, Kasai K, Iwamoto K. DNA methylation in schizophrenia: progress and challenges of epigenetic studies. Genome Med. 2012;4(12):96.
Kriaucionis S, Heintz N. The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science. 2009;324(5929):929-930.
Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;324(5929):930-935.
He YF, Li BZ, Li Z, Liu P, Wang Y, Tang Q, et al. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science. 2011;333(6047):1303-1307.
Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, et al. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science. 2011;333(6047):1300-1303.
Kato T, Iwamoto K. Comprehensive DNA methylation and hydroxymethylation analysis in the human brain and its implication in mental disorders. Neuropharmacology. 2014;80:133-139.
Szyf M. The elusive role of 5′-hydroxymethylcytosine. Epigenomics. 2016;8(11):1539-1551.
Globisch D, Münzel M, Müller M, Michalakis S, Wagner M, Koch S, et al. Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates. PLoS One. 2010;5(12):e15367.
Li W, Liu M. Distribution of 5-hydroxymethylcytosine in different human tissues. J Nucleic Acids. 2011;2011:1-5.
Chen Y, Damayanti NP, Irudayaraj J, Dunn K, Zhou FC. Diversity of two forms of DNA methylation in the brain. Front Genet. 2014;5:46.
Hahn MA, Qiu R, Wu X, Li AX, Zhang H, Wang J, et al. Dynamics of 5-hydroxymethylcytosine and chromatin marks in mammalian neurogenesis. Cell Rep. 2013;3(2):291-300.
Song CX, Szulwach KE, Fu Y, Dai Q, Yi C, Li X, et al. Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine. Nat Biotechnol. 2011;29(1):68-72.
Szulwach KE, Li X, Li Y, Song CX, Wu H, Dai Q, et al. 5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging. Nat Neurosci. 2011;14(12):1607-1616.
Lister R, Mukamel EA, Nery JR, Urich M, Puddifoot CA, Johnson ND, et al. Global epigenomic reconfiguration during mammalian brain development. Science. 2013;341(6146):1237905.
Wagner M, Steinbacher J, Kraus TF, et al. Age-dependent levels of 5-methyl-, 5-hydroxymethyl-, and 5-formylcytosine in human and mouse brain tissues. Angew Chem Int ed Engl. 2015;54(42):12511-12514.
Al-Mahdawi S, Virmouni SA, Pook MA. The emerging role of 5-hydroxymethylcytosine in neurodegenerative diseases. Front Neurosci. 2014;8:397.
Bundo M, Ueda J, Nakachi Y, Kasai K, Kato T, Iwamoto K. Decreased DNA methylation at promoters and gene-specific neuronal hypermethylation in the prefrontal cortex of patients with bipolar disorder. Mol Psychiatry. 2021;26(7):3407-3418.
Cheng Y, Bernstein A, Chen D, Jin P. 5-hydroxymethylcytosine: a new player in brain disorders? Exp Neurol. 2015;268:3-9.
Murata Y, Ikegame T, Koike S, Saito T, Ikeda M, Sasaki T, et al. Global DNA hypomethylation and its correlation to the betaine level in peripheral blood of patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2020;99:109855.
Karimi M, Johansson S, Stach D, Corcoran M, Grandér D, Schalling M, et al. LUMA (luminometric methylation assay)-a high throughput method to the analysis of genomic DNA methylation. Exp Cell Res. 2006;312(11):1989-1995.
Sugawara H, Iwamoto K, Bundo M, Ueda J, Ishigooka J, Kato T. Comprehensive DNA methylation analysis of human peripheral blood leukocytes and lymphoblastoid cell lines. Epigenetics. 2011;6(4):508-515.
Guevara EE, Hopkins WD, Hof PR, Ely JJ, Bradley BJ, Sherwood CC. Epigenetic ageing of the prefrontal cortex and cerebellum in humans and chimpanzees. Epigenetics. 2022;17:1774-1785.
Feng J, Shao N, Szulwach KE, Vialou V, Huynh J, Zhong C, et al. Role of Tet1 and 5-hydroxymethylcytosine in cocaine action. Nat Neurosci. 2015;18(4):536-544.
Jayanthi S, Gonzalez B, McCoy MT, Ladenheim B, Bisagno V, Cadet JL. Methamphetamine induces TET1- and TET3-dependent DNA hydroxymethylation of Crh and Avp genes in the rat nucleus accumbens. Mol Neurobiol. 2018;55(6):5154-5166.