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Plasma cell differentiation is coupled to division-dependent DNA hypomethylation and gene regulation
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Plasma cell differentiation is coupled to division-dependent DNA hypomethylation and gene regulation
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Journal Article
Plasma cell differentiation is coupled to division-dependent DNA hypomethylation and gene regulation
2016
Overview
Boss and colleagues provide mechanistic insight into cell-division-coupled transcriptional and epigenetic reprogramming events during plasma cell differentiation.
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-κB 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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 45
/ 45/91
/ Animals
/ Cell Differentiation - genetics
/ DNA
/ Female
/ Immunity, Humoral - genetics
/ Interferon Regulatory Factors - genetics
/ Interferon Regulatory Factors - metabolism
/ Male
/ Mice
/ Octamer Transcription Factor-2 - genetics
/ Octamer Transcription Factor-2 - metabolism
/ resource
