@article{eb506fed8105449dbfdb5c4c2edda6ae,
title = "5-hmC in the brain is abundant in synaptic genes and shows differences at the exon-intron boundary",
abstract = "The 5-methylcytosine (5-mC) derivative 5-hydroxymethylcytosine (5-hmC) is abundant in the brain for unknown reasons. Here we characterize the genomic distribution of 5-hmC and 5-mC in human and mouse tissues. We assayed 5-hmC by using glucosylation coupled with restriction-enzyme digestion and microarray analysis. We detected 5-hmC enrichment in genes with synapse-related functions in both human and mouse brain. We also identified substantial tissue-specific differential distributions of these DNA modifications at the exon-intron boundary in human and mouse. This boundary change was mainly due to 5-hmC in the brain but due to 5-mC in non-neural contexts. This pattern was replicated in multiple independent data sets and with single-molecule sequencing. Moreover, in human frontal cortex, constitutive exons contained higher levels of 5-hmC relative to alternatively spliced exons. Our study suggests a new role for 5-hmC in RNA splicing and synaptic function in the brain.",
author = "Tarang Khare and Shraddha Pai and Karolis Koncevicius and Mrinal Pal and Edita Kriukiene and Zita Liutkeviciute and Manuel Irimia and Peixin Jia and Carolyn Ptak and Menghang Xia and Raymond Tice and Mamoru Tochigi and Solange Mor{\'e}ra and Anaies Nazarians and Denise Belsham and Wong, {Albert H.C.} and Blencowe, {Benjamin J.} and Wang, {Sun Chong} and Philipp Kapranov and Rafal Kustra and Viviane Labrie and Saulius Klimasauskas and Arturas Petronis",
note = "Funding Information: of Toronto and by the Ontario Mental Health Foundation. M.I. is supported by a Human Frontier Science Program Organization Long Term Fellowship. Funding Information: We thank N. Miller and C. Austin (National Center for Advancing Translational Sciences, US National Institutes of Health, Bethesda, Maryland, USA) for providing cell lines for the SAHA experiment. We also thank J.-S. Doucet (Centre for Addiction and Mental Health Toronto, Canada) for assistance with mouse brain sample preparation. This research has been supported by the Canadian Institutes of Health Research (grants 199170 and 186007) and the US National Institutes of Health (grants MH074127, MH088413, DP3DK085698, HG005758 and HG004535) to A.P. and Canadian Institutes of Health Research grants to B.J.B., by the Research Council of Lithuania and the French Ministry of Foreign and European affairs under the Lithuania-France bilateral collaboration program Gilibert (grant TAP-13/2011–2012) to S.M. and S.K., and by the European Social Fund under the Global Grant measure (grant VP1-3.1-{\v S}MM-07-K-01-105) to S.K. A.P. is supported as a Tapscott Chair in Schizophrenia Studies at the University",
year = "2012",
month = oct,
doi = "10.1038/nsmb.2372",
language = "???core.languages.en_GB???",
volume = "19",
pages = "1037--1044",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
number = "10",
}