title: Genome-wide DNA methylation analysis in precursor B-cells.
abstract: 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.
authors.affiliation: a Department of Pathology and Anatomical Sciences ; University of Missouri-Columbia ; Columbia , MO USA.
authors.forename: Md
authors.initials: M
authors.lastname: Almamun
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Levinson
authors.forename: Susan T
authors.initials: ST
authors.lastname: Gater
authors.forename: Robert D
authors.initials: RD
authors.lastname: Schnabel
authors.forename: Gerald L
authors.initials: GL
authors.lastname: Arthur
authors.forename: J Wade
authors.initials: JW
authors.lastname: Davis
authors.forename: Kristen H
authors.initials: KH
authors.lastname: Taylor
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D018899:CpG Islands; D019175:DNA Methylation; D005312:Fetal Blood / Q000166:cytology; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007231:Infant, Newborn; D016131:Lymphocyte Subsets; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology; D054448:Precursor Cells, B-Lymphoid / Q000502:physiology*
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