Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.37 (DNA methyltransferase)
 4,983 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DNA methylation-mediated regulation drives and stabilizes transcription states throughout development. In myeloid differentiation, DNA methylation changes occur predominantly in the direction towards hypomethylation. Also, in vitro differentiation of monocytes to dendritic cells and macrophages is characterized by DNA demethylation. In this study, we identified the existence of methylation changes in the direction of hypermethylation among genes that become repressed during monocyte-to-dendritic cell differentiation. We identified the acquisition of DNA methylation in genes such as CSF3R, FYN, and CX3CR1, but not in others, such as CD14. Analysis of the dynamics of methylation and expression changes of these genes revealed that loss of expression was rapid and was associated with the loss of H3K4me3 and H3K36me3, whereas gains of DNA methylation were progressive and partially concomitant with increases in H3K9me3 and H3K27me3. Inhibition of DNA methyltransferases, with the DNA replication-independent drug nanaomycin A, revealed that there were no effects on expression and H3K4me3 changes, despite the partial impairment of DNA methylation and H3K27me3 acquisition. However, cells treated with the DNA methyltransferase inhibitor showed lower levels of dendritic cell surface markers, suggesting a potential effect on the stability of the differentiated phenotype. Our data give rise to a novel perspective on the functional relevance and mechanisms of the acquisition of DNA methylation in myeloid cell differentiation.
 ...
PMID:Gains of DNA methylation in myeloid terminal differentiation are dispensable for gene silencing but influence the differentiated phenotype. 2521 24

Molecular characterizations, including microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP) showed strong associations in colorectal carcinoma (CRC) and provided a deeper understanding of the etiology of disease. However, the global relationship between epigenetic alternations and changes in mRNA expression in CRC remains largely undefined, especially regarding the roles of DNA methyltransferases (DNMTs). Here, we conducted a systematic network comparison to explore the global conservation between co-expressed and co-methylated modules. We successfully identified immune-related modules that were regulated by DNMTs and had strong associations with immune-infiltrating neutrophils and dendritic cells in CRC. Moreover, we found that genes in those modules were prognostic for CRC, with 97.1% (168/173) being significantly influenced by DNMTs. Thus, this study resolved an interaction between DNA methylation and mRNA expression through DNMTs. Additionally, we provided evidence that DNMTs control the global hypomethylation of oncogenes, including ALOX5AP and CSF3R that otherwise have high methylation in normal colons. Such genes were also more sensitive to DNMT changes, such as in CRC. Collectively, our analyzes provided a systems biology approach to investigate the association among different molecular phenotypes in diseases.
 ...
PMID:Integrative analysis identifies DNMTs against immune-infiltrating neutrophils and dendritic cells in colorectal cancer. 3088 May 52