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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.

SUBMITTER: Khare T

PROVIDER: S-EPMC3465469 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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5-hmC in the brain is abundant in synaptic genes and shows differences at the exon-intron boundary.

Khare Tarang T Pai Shraddha S Koncevicius Karolis K Pal Mrinal M Kriukiene Edita E Liutkeviciute Zita Z Irimia Manuel M Jia Peixin P Ptak Carolyn C Xia Menghang M Tice Raymond R Tochigi Mamoru M Moréra Solange S Nazarians Anaies A Belsham Denise D Wong Albert H C AH Blencowe Benjamin J BJ Wang Sun Chong SC Kapranov Philipp P Kustra Rafal R Labrie Viviane V Labrie Viviane V Klimasauskas Saulius S Petronis Arturas A

Nature structural & molecular biology 20120909 10

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 D ...[more]

PMID: 22961382

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Project description:5-hydroxymethylcytosine (5-hmC), a derivative of 5-methylcytosine (5-mC), is abundant in the brain for unknown reasons. We mapped the genomic distribution of 5-hmC and 5-mC in human and mouse tissues using glucosylation of 5-hmC coupled with restriction enzyme digestion, and interrogation on microarrays. We detected 5-hmC enrichment in genes with synapse-related functions in the brain. We also identified significant, tissue-specific differential distributions of these DNA modifications at the exon-intron boundary, in both 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 datasets, and the brain-specific change in 5-hmC was validated using single-molecule sequencing. Moreover, in the brain, constitutive exons contained higher levels of 5-hmC, relative to alternatively-spliced exons. Our study suggests a novel role for 5-hmC in RNA splicing and synaptic function in the brain The M-NM-2-glucosyltransferase (BGT) enzyme transfers a glucose molecule specifically to the hydroxymethyl group of 5-hmC, thus rendering it resistant to digestion by the methylation insensitive MspI enzyme at the ChmCGG target site; 5-hmC is thus detected by differential resistance to MspI-digestion with and without glucosylation of genomic DNA (gDNA). HpaII (targets the same site, CCGG) cannot cut CmCGG or ChmCGG, and conceptually its difference with MspI digestion is a measure of both 5-mC and 5-hmC. Subtraction of 5-hmC from the HpaII-based estimate therefore measures 5-mC. These estimates were measured on respective Affymetrix whole-genome tiling arrays (2.0 R ) MspI - APRIL_fc1.ch02_coverage.bed Undigested DNA - APRIL_fc1.ch01_coverage.bed GluMspI - APRIL_fc1.ch04_coverage_NONTARGET.bed GluMspI - APRIL_fc1.ch04_coverage.bed MspI - APRIL_fc1.ch02_coverage_NONTARGET.bed Undigested DNA - APRIL_fc1.ch01_coverage_NONTARGET.bed MspI - MARCH_fc1.ch02_coverage_NONTARGET.bed Undigested DNA - MARCH_fc1.ch01_coverage_NONTARGET.bed GluMspI - MARCH_fc1.ch04_coverage_NONTARGET.bed GluMspI - MARCH_fc1.ch04_coverage.bed MspI - MARCH_fc1.ch02_coverage.bed Undigested DNA - MARCH_fc1.ch01_coverage.bed MspI - MAY_fc1.ch02_coverage.bed GluMspI - MAY_fc1.ch04_coverage_NONTARGET.bed GluMspI - MAY_fc1.ch04_coverage.bed Undigested DNA - MAY_fc1.ch01_coverage.bed MspI - MAY_fc1.ch02_coverage_NONTARGET.bed Undigested DNA - MAY_fc1.ch01_coverage_NONTARGET.bed

Dataset Information

5-hmC in the brain is abundant in synaptic genes and shows differences at the exon-intron boundary.

Publications

5-hmC in the brain is abundant in synaptic genes and shows differences at the exon-intron boundary.

Similar Datasets

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