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 naïve-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 naïve 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.
Keywords: CG dinucleotide; CLP, common lymphoid progenitor cells; CpGI, CpG island; DMRs, differentially methylated regions; DNA methylation; FDR, false discovery rate.; H3K27ac, histone H3 lysine 27 acetylation; H3K4me1, histone H3 lysine 4 monomethylation; HCB, human umbilical cord blood; HSCs, haematopoietic stem cells; MBDs, methyl CpG binding domains; MIRA-seq, methylated CpG island recovery assay (MIRA) followed by next generation sequencing; MeCP2, methyl CpG binding protein 2; Pre-B, precursor B-cell; CD; Pro-B, progenitor B-cell; ROIs, regions of interest; TFs, transcription factors; acute lymphoblastic leukemia; CpG; cluster of differentiation; ALL; enhancer; next-generation sequencing; precursor B-cell; umbilical cord blood.