title: Plasma cell differentiation is coupled to division-dependent DNA hypomethylation and gene regulation.
abstract: 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.
authors: Department of Microbiology & Immunology Emory University School of Medicine Atlanta, GA, USA.
authors: Benjamin G
authors: BG
authors: Barwick
authors: Department of Microbiology & Immunology Emory University School of Medicine Atlanta, GA, USA.
authors: Christopher D
authors: CD
authors: Scharer
authors: Department of Microbiology & Immunology Emory University School of Medicine Atlanta, GA, USA.
authors: Alexander P R
authors: APR
authors: Bally
authors: Department of Microbiology & Immunology Emory University School of Medicine Atlanta, GA, USA.
authors: Jeremy M
authors: JM
authors: Boss
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D001665:Binding Sites / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D056724:Immunity, Humoral / Q000235:genetics; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D050813:Octamer Transcription Factor-2 / Q000235:genetics / Q000378:metabolism; D010950:Plasma Cells / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D050835:Interferon Regulatory Factors; D016328:NF-kappa B; D050813:Octamer Transcription Factor-2; D018808:Transcription Factor AP-1