Gene-body 5-hydroxymethylation is associated with gene expression changes in the prefrontal cortex of depressed individuals.
Transl Psychiatry
; 7(5): e1119, 2017 05 09.
Article
em En
| MEDLINE
| ID: mdl-28485726
ABSTRACT
5-Hydroxymethylcytosine (5hmC) is a recently characterized epigenetic mark that is particularly abundant in brain tissue and that regulates gene transcription. We have recently begun to understand the important role of 5hmC in brain development, plasticity and disease, but there are currently little data on 5hmC alterations in psychiatric illnesses. Here we report what we believe to be the first genome-wide analysis of 5hmC in the depressed brain. Using AbaSI sequencing, we investigated 5hmC in the prefrontal cortex of depressed (N=19) and psychiatrically healthy controls (N=19). Consistent with previous global 5hmC analyses in other phenotypes, and likely owing to the inter-individual variability in 5hmC content, the distribution of 5hmC across chromosomes and genomic features was not different between groups. We did, however, find 550 CpGs with suggestive evidence of differential hydroxymethylation. Of these, we validated CpGs in the gene body of myosin XVI (MYO16) and insulin-degrading enzyme using targeted oxidative bisulfite sequencing. Furthermore, the enrichment of 5hmC was also associated with changes in the expression of these two genes in depressed suicides. Together, our results present a novel mechanism linking increased 5hmC to depression and provide a framework for future research in this field.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Expressão Gênica
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Córtex Pré-Frontal
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5-Metilcitosina
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Transtorno Depressivo Maior
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Transl Psychiatry
Ano de publicação:
2017
Tipo de documento:
Article