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A global DNA methylation and gene expression analysis of early human B-cell development reveals a demethylation signature and transcription factor network. Nucleic Acids Res. 2012 Dec;40(22):11339-51. We examined DNA methylation and RNA expression status during early B-cell development by sorting multiple replicates of four separate stages of pre-B cells derived from normal human fetal bone marrow and applied high-dimension DNA methylation scanning and expression arrays. We identified a distinct development-dependent demethylation signature which has gene expression regulatory properties for pre-B cells, and provide a catalog reference for the epigenetic changes that occur in pre-B-cell leukemia and other B-cell-related diseases. Human fetal bone marrow was obtained, and using flow cytometry antibodies, four populations of B-cell developmental stages including stage 1 (S1; predominantly multipotent progenitors before lineage commitment and common lymphoid progenitors), stage II (S2; pre-B-I cells), stage 3 (S3; pre-B-II cells) and stage 4 cells (S4; immature B cells). For 8 indibiduals, DNAs and RNAs were isolated and the methylation and expression changes during early B-cell development were identified using the Illumina HumanMethylation450 Beadchip (Illumina) and GeneChip Human Gene 1.0 ST Array (Affymetrix).

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