Journal
NATURE IMMUNOLOGY
Volume 17, Issue 10, Pages 1216-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3519
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Funding
- Emory University School of Medicine
- US National Institutes of Health [R01 GM47310, R01 AI123733, U19 AI110483, F31 AI112261, T32 GM008490, T32 AI007610]
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The epigenetic processes that regulate antibody-secreting plasma cells are not well understood. Here, analysis of plasma cell differentiation revealed DNA hypomethylation of 10% of CpG loci that were overrepresented at enhancers. Inhibition of DNA methylation enhanced plasma cell commitment in a cell-division-dependent manner. Analysis of B cells differentiating in vivo stratified by cell division revealed a fivefold increase in mRNA transcription coupled to DNA hypomethylation. Demethylation occurred first at binding motifs for the transcription factors NF-kappa B and AP-1 and later at those for the transcription factors IRF and Oct-2 and was coincident with activation and differentiation gene-expression programs in a cell-division-dependent manner. These data provide mechanistic insight into cell-division-coupled transcriptional and epigenetic reprogramming and suggest that DNA hypomethylation reflects the cis-regulatory history of plasma cell differentiation.
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