期刊
EPIGENETICS
卷 9, 期 12, 页码 1588-1595出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/15592294.2014.983379
关键词
DNA methylation; enhancer; next-generation sequencing; precursor B-cell; umbilical cord blood; HCB; human umbilical cord blood; HSCs; haematopoietic stem cells; CLP; common lymphoid progenitor cells; Pro-B; progenitor B-cell; Pre-B; precursor B-cell; CD; cluster of differentiation; ALL; acute lymphoblastic leukemia; CpG; CG dinucleotide; CpGI; CpG island; MIRA-seq; methylated CpG island recovery assay (MIRA) followed by next generation sequencing; TFs; transcription factors; MBDs; methyl CpG binding domains; MeCP2; methyl CpG binding protein 2; DMRs; differentially methylated regions; ROIs; regions of interest; H3K4me1; histone H3 lysine 4 monomethylation; H3K27ac; histone H3 lysine 27 acetylation; FDR; false discovery rate
资金
- National Institutes of Health [NCI R00 CA132784]
DNA methylation is responsible for regulating gene expression and cellular differentiation and for maintaining genomic stability during normal human development. Furthermore, it plays a significant role in the regulation of hematopoiesis. In order to elucidate the influence of DNA methylation during B-cell development, genome-wide DNA methylation status of pro-B, pre-BI, pre-BII, and naive-B-cells isolated from human umbilical cord blood was determined using the methylated CpG island recovery assay followed by next generation sequencing. On average, 182-200 million sequences were generated for each precursor B-cell subset in 10 biological replicates. An overall decrease in methylation was observed during the transition from pro-B to pre-BI, whereas no differential methylation was observed in the pre-BI to pre-BII transition or in the pre-BII to naive B-cell transition. Most of the methylated regions were located within intergenic and intronic regions not present in a CpG island context. Putative novel enhancers were identified in these regions that were differentially methylated between pro-B and pre-BI cells. The genome-wide methylation profiles are publically available and may be used to gain a better understanding of the involvement of atypical DNA methylation in the pathogenesis of malignancies associated with precursor B-cells.
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