Characterization of the genetic determinants of context-specific DNA methylation in primary monocytes.
Cell Genom
; 4(5): 100541, 2024 May 08.
Article
em En
| MEDLINE
| ID: mdl-38663408
ABSTRACT
To better understand inter-individual variation in sensitivity of DNA methylation (DNAm) to immune activity, we characterized effects of inflammatory stimuli on primary monocyte DNAm (n = 190). We find that monocyte DNAm is site-dependently sensitive to lipopolysaccharide (LPS), with LPS-induced demethylation occurring following hydroxymethylation. We identify 7,359 high-confidence immune-modulated CpGs (imCpGs) that differ in genomic localization and transcription factor usage according to whether they represent a gain or loss in DNAm. Demethylated imCpGs are profoundly enriched for enhancers and colocalize to genes enriched for disease associations, especially cancer. DNAm is age associated, and we find that 24-h LPS exposure triggers approximately 6 months of gain in epigenetic age, directly linking epigenetic aging with innate immune activity. By integrating LPS-induced changes in DNAm with genetic variation, we identify 234 imCpGs under local genetic control. Exploring shared causal loci between LPS-induced DNAm responses and human disease traits highlights examples of disease-associated loci that modulate imCpG formation.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Monócitos
/
Ilhas de CpG
/
Metilação de DNA
/
Epigênese Genética
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Cell Genom
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Reino Unido