Characterizing 5-hydroxymethylcytosine in human prefrontal cortex at single base resolution.
|Title||Characterizing 5-hydroxymethylcytosine in human prefrontal cortex at single base resolution.|
|Publication Type||Journal Article|
|Year of Publication||2015|
|Authors||Gross JA, Pacis A, Chen GG, Barreiro LB, Ernst C, Turecki G|
|Date Published||2015 Sep 03|
|Keywords||Adult, Base Pairing, Binding Sites, Chromosomes, Human, Cluster Analysis, Cytosine, Epigenesis, Genetic, Exons, Female, Gene Ontology, Genome, Human, Humans, Introns, Male, Prefrontal Cortex, Protein Processing, Post-Translational, Sequence Analysis, DNA, Sex Characteristics, X Chromosome Inactivation|
BACKGROUND: The recent discovery that methylated cytosines are converted to 5-hydroxymethylated cytosines (5hmC) by the family of ten-eleven translocation enzymes has sparked significant interest on the genomic location, the abundance in different tissues, the putative functions, and the stability of this epigenetic mark. 5hmC plays a key role in the brain, where it is particularly abundant and dynamic during development.RESULTS: Here, we comprehensively characterize 5hmC in the prefrontal cortices of 24 subjects. We show that, although there is inter-individual variability in 5hmC content among unrelated individuals, approximately 8 % of all CpGs on autosomal chromosomes contain 5hmC, while sex chromosomes contain far less. Our data also provide evidence suggesting that 5hmC has transcriptional regulatory properties, as the density of 5hmC was highest in enhancer regions and within exons. Furthermore, we link increased 5hmC density to histone modification binding sites, to the gene bodies of actively transcribed genes, and to exon-intron boundaries. Finally, we provide several genomic regions of interest that contain gender-specific 5hmC.CONCLUSIONS: Collectively, these results present an important reference for the growing number of studies that are interested in the investigation of the role of 5hmC in brain and mental disorders.
|Alternate Journal||BMC Genomics|
|PubMed Central ID||PMC4559220|
|Grant List||MOP119429 / / PHS HHS / United States |
R01 DA033684 / DA / NIDA NIH HHS / United States
MOP119429 / / Medical Research Council / United Kingdom
MOP93775 / / Medical Research Council / United Kingdom
MOP11260 / / Medical Research Council / United Kingdom
MOP119430 / / Medical Research Council / United Kingdom