Dynamic epigenome of differentiation and maturation of human dendritic cells
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摘要
Objective: Combinatorial epigenetic regulationis critical to maintain unique cell identity. However, dynamic epigenomes of human primary cells, particularly immune cell lineages undergoing differentiation, have rarely been reported. Methods: Using human primary lineage of monocytes, monocyte-derived immature dendritic cells(im DCs) and LPSmatured DCs(m DCs) representing the dynamic process of antigen-presenting cell differentiation and maturation, we established base-resolution DNA methylomes, H3K4me3 and H3K27me3 maps and mRNA transcriptome of this dynamic lineage.Results: Comparative analysis of dynamic epigenomic patterns revealed that DNA demethylation during monocytes differentiation into im DCs and de novo methylation during DCs maturation are DC-dominant DNA methylation variations. These genome-wide differential DNA methylation regions(DMRs) are mostly outside CpG islands. Conclusion: For histone modifications, H3K27me3 has the same dynamic pattern with DNA methylation, while H3K-4me3 has a constant increased pattern. Furthermore, H3K27me3 has similar variation trends with DNA methylation both across these DC-dominant DMRs and in the DMR-associated gene loci.
Objective: Combinatorial epigenetic regulationis critical to maintain unique cell identity. However, dynamic epigenomes of human primary cells, particularly immune cell lineages undergoing differentiation, have rarely been reported. Methods: Using human primary lineage of monocytes, monocyte-derived immature dendritic cells(im DCs) and LPSmatured DCs(m DCs) representing the dynamic process of antigen-presenting cell differentiation and maturation, we established base-resolution DNA methylomes, H3K4me3 and H3K27me3 maps and mRNA transcriptome of this dynamic lineage.Results: Comparative analysis of dynamic epigenomic patterns revealed that DNA demethylation during monocytes differentiation into im DCs and de novo methylation during DCs maturation are DC-dominant DNA methylation variations. These genome-wide differential DNA methylation regions(DMRs) are mostly outside Cp G islands. Conclusion: For histone modifications, H3K27me3 has the same dynamic pattern with DNA methylation, while H3K-4me3 has a constant increased pattern. Furthermore, H3K27me3 has similar variation trends with DNA methylation both across these DC-dominant DMRs and in the DMR-associated gene loci.
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