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.
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PMID:Gains of DNA methylation in myeloid terminal differentiation are dispensable for gene silencing but influence the differentiated phenotype. 2521 24

MicroRNAs (miRs) involve in osteogenic differentiation and osteogenic potential of mesenchymal stem cells (MSCs). Accordingly, the present study aimed to further uncover role miR-149 plays in osteogenic differentiation of MSCs with the involvement of the stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) pathway. Initially, the osteogenic differentiation model was induced. Next, the positive expression of STRO-1 in periosteum, alkaline phosphatase (ALP) activity, osteocalcin (OCN) protein content, and the calcium deposition in MSCs were determined. MSCs were treated with DNA methyltransferase inhibitor 5-aza-CdR, SDF-1 neutralizing antibody, or CXCR4 antagonist AMD3100 to investigate their roles in osteogenic differentiation; with the expression of CD44, CD90, CD14, and CD45 detected. Furthermore, the levels of SDF-1 and CXCR4, and the genes related to stemness (Nanog, Oct-4, and Sox-2) were measured to explore the effects of miR-149. The obtained data revealed the upregulation of STRO-1 in the periosteum. miR-149 could specifically bind to SDF-1. Besides, increased miR-149 methylation, higher ALP activity and OCN content, decreased positive rates of CD44 and CD90, and increased positive rates of CD14 and CD45 were found in osteogenic differentiation of MSCs. Subsequently, 5-Aza-CdR treatment reversed the above-mentioned effects. MSCs were finally treated with SDF-1 neutralizing antibody or AMD3100 to decrease Nanog, Oct-4, and Sox-2 expression. Taken together these results, miR-149 hypermethylation has the potential to activate the SDF-1/CXCR4 pathway and further promote osteogenic differentiation of MSCs.
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PMID:Hypermethylation of microRNA-149 activates SDF-1/CXCR4 to promote osteogenic differentiation of mesenchymal stem cells. 3120 87