A global DNA methylation and gene expression analysis of early human B-cell development reveals a demethylation signature and transcription factor network.

A global DNA methylation and gene expression analysis of early human B-cell development reveals a demethylation signature and transcription factor network.
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DOI:
10.1093/nar/gks957
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发表时间:
2012-12
影响因子:
14.9
通讯作者:
Wiemels JL
Wiemels JL
中科院分区:
生物学2区
文献类型:
--
作者:
Lee ST;Xiao Y;Muench MO;Xiao J;Fomin ME;Wiencke JK;Zheng S;Dou X;de Smith A;Chokkalingam A;Buffler P;Ma X;Wiemels JL

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The epigenetic changes during B-cell development relevant to both normal function and hematologic malignancy are incompletely understood. 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. Features of promoter and gene body DNA methylation were strongly correlated with RNA expression in multipotent progenitors (MPPs) both in a static state and throughout differentiation. As MPPs commit to pre-B cells, a predominantly demethylating phenotype ensues, with 79% of the 2966 differentially methylated regions observed involving demethylation. Demethylation events were more often gene body associated rather than promoter associated; predominantly located outside of CpG islands; and closely associated with EBF1, E2F, PAX5 and other functional transcription factor (TF) sites related to B-cell development. Such demethylation events were accompanied by TF occupancy. After commitment, DNA methylation changes appeared to play a smaller role in B-cell development. 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.
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