Characterizing 5-hydroxymethylcytosine in human prefrontal cortex at single base resolution.
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.
McGill Group for Suicide Studies, Douglas Mental Health University Institute, 6875 boul. Lasalle, Montreal, Quebec, Canada. jeffrey.gross@mail.mcgill.ca.
Jeffrey A
JA
Gross
Department of Genetics, CHU Sainte-Justine Research Centre, 3175 Chemin de la Côte-Sainte-Catherine, Montreal, Quebec, Canada. vapacis@gmail.com.|Departments of Biochemistry and Pediatrics, University of Montreal, 2900 Boulevard Edouard-Montpetit, Montreal, Quebec, Canada. vapacis@gmail.com.
Alain
A
Pacis
McGill Group for Suicide Studies, Douglas Mental Health University Institute, 6875 boul. Lasalle, Montreal, Quebec, Canada. gang.chen@douglas.mcgill.ca.
Gary G
GG
Chen
Department of Genetics, CHU Sainte-Justine Research Centre, 3175 Chemin de la Côte-Sainte-Catherine, Montreal, Quebec, Canada. luis.barreiro@umontreal.ca.|Departments of Biochemistry and Pediatrics, University of Montreal, 2900 Boulevard Edouard-Montpetit, Montreal, Quebec, Canada. luis.barreiro@umontreal.ca.
Luis B
LB
Barreiro
McGill Group for Suicide Studies, Douglas Mental Health University Institute, 6875 boul. Lasalle, Montreal, Quebec, Canada. carl.ernst@mcgill.ca.
Carl
C
Ernst
McGill Group for Suicide Studies, Douglas Mental Health University Institute, 6875 boul. Lasalle, Montreal, Quebec, Canada. gustavo.turecki@mcgill.ca.
Gustavo
G
Turecki
D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000328:Adult; D020029:Base Pairing; D001665:Binding Sites / Q000235:genetics; D002877:Chromosomes, Human / Q000378:metabolism; D016000:Cluster Analysis; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D044127:Epigenesis, Genetic; D005091:Exons / Q000235:genetics; D005260:Female; D063990:Gene Ontology; D015894:Genome, Human; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D017397:Prefrontal Cortex / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017422:Sequence Analysis, DNA; D012727:Sex Characteristics; D049951:X Chromosome Inactivation / Q000235:genetics
C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine