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Title: 5-hmC in the brain: abundance in synaptic genes and differences at the exon-intron boundary (MRE-Seq)      
dateReleased:
08-24-2012
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 β-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
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-40158
refinement:
raw
alternateIdentifiers:
40158
keywords:
functional genomics
dateModified:
06-02-2014
availability:
available
types:
gene expression
name:
Homo sapiens
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-40158/E-GEOD-40158.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-40158/E-GEOD-40158.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE40158
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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