Plasma cell differentiation is controlled by multiple cell division-coupled epigenetic programs

The genomic loci associated with B cell differentiation that are subject to transcriptional and epigenetic regulation in vivo are not well defined, leaving a gap in our understanding of the development of humoral immune responses. Here, using an in vivo T cell independent B cell differentiation mode...

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Published inNature communications Vol. 9; no. 1; pp. 1698 - 14
Main Authors Scharer, Christopher D., Barwick, Benjamin G., Guo, Muyao, Bally, Alexander P. R., Boss, Jeremy M.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 27.04.2018
Nature Publishing Group
Nature Portfolio
Subjects
13/31
38/39
45/15
45/91
631/250/2502/2170
631/337/100
64/60
Accessibility
Animals
Cell differentiation
Cell Differentiation - genetics
Cell division
Cell Division - genetics
Cell Line, Tumor
Chromatin
Differentiation (biology)
DNA Methylation - genetics
Enhancer of Zeste Homolog 2 Protein - antagonists & inhibitors
Enhancer of Zeste Homolog 2 Protein - genetics
Enhancer of Zeste Homolog 2 Protein - metabolism
Epigenesis, Genetic - genetics
Epigenetics
Gene expression
Gene regulation
Genes
Histones - metabolism
Humanities and Social Sciences
Immune response (humoral)
Immunity, Humoral - genetics
Kinases
Lymphocytes B
Lymphocytes T
Metabolism
Mice, Inbred C57BL
Mice, Transgenic
multidisciplinary
Plasma
Plasma cells
Plasma Cells - physiology
Positive Regulatory Domain I-Binding Factor 1 - genetics
Positive Regulatory Domain I-Binding Factor 1 - metabolism
Primary Cell Culture
Promoter Regions, Genetic - genetics
Science
Science (multidisciplinary)
Online AccessGet full text

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Abstract The genomic loci associated with B cell differentiation that are subject to transcriptional and epigenetic regulation in vivo are not well defined, leaving a gap in our understanding of the development of humoral immune responses. Here, using an in vivo T cell independent B cell differentiation model, we define a cellular division-dependent cis -regulatory element road map using ATAC-seq. Chromatin accessibility changes correlate with gene expression and reveal the reprogramming of transcriptional networks and the genes they regulate at specific cell divisions. A subset of genes in naive B cells display accessible promoters in the absence of transcription and are marked by H3K27me3, an EZH2 catalyzed repressive modification. Such genes encode regulators of cell division and metabolism and include the essential plasma cell transcription factor Blimp-1. Chemical inhibition of EZH2 results in enhanced plasma cell formation, increased expression of the above gene set, and premature expression of Blimp-1 ex vivo. These data provide insights into cell-division coupled epigenetic and transcriptional processes that program plasma cells. During B cell differentiation, the role of different genomic loci in transcriptional and epigenetic regulation in vivo is not well defined. Here the authors use an in vivo B cell differentiation model to map cellular division-dependent cis -regulatory element road map with ATAC-seq.
AbstractList The genomic loci associated with B cell differentiation that are subject to transcriptional and epigenetic regulation in vivo are not well defined, leaving a gap in our understanding of the development of humoral immune responses. Here, using an in vivo T cell independent B cell differentiation model, we define a cellular division-dependent cis-regulatory element road map using ATAC-seq. Chromatin accessibility changes correlate with gene expression and reveal the reprogramming of transcriptional networks and the genes they regulate at specific cell divisions. A subset of genes in naive B cells display accessible promoters in the absence of transcription and are marked by H3K27me3, an EZH2 catalyzed repressive modification. Such genes encode regulators of cell division and metabolism and include the essential plasma cell transcription factor Blimp-1. Chemical inhibition of EZH2 results in enhanced plasma cell formation, increased expression of the above gene set, and premature expression of Blimp-1 ex vivo. These data provide insights into cell-division coupled epigenetic and transcriptional processes that program plasma cells.
The genomic loci associated with B cell differentiation that are subject to transcriptional and epigenetic regulation in vivo are not well defined, leaving a gap in our understanding of the development of humoral immune responses. Here, using an in vivo T cell independent B cell differentiation model, we define a cellular division-dependent cis -regulatory element road map using ATAC-seq. Chromatin accessibility changes correlate with gene expression and reveal the reprogramming of transcriptional networks and the genes they regulate at specific cell divisions. A subset of genes in naive B cells display accessible promoters in the absence of transcription and are marked by H3K27me3, an EZH2 catalyzed repressive modification. Such genes encode regulators of cell division and metabolism and include the essential plasma cell transcription factor Blimp-1. Chemical inhibition of EZH2 results in enhanced plasma cell formation, increased expression of the above gene set, and premature expression of Blimp-1 ex vivo. These data provide insights into cell-division coupled epigenetic and transcriptional processes that program plasma cells. During B cell differentiation, the role of different genomic loci in transcriptional and epigenetic regulation in vivo is not well defined. Here the authors use an in vivo B cell differentiation model to map cellular division-dependent cis -regulatory element road map with ATAC-seq.
The genomic loci associated with B cell differentiation that are subject to transcriptional and epigenetic regulation in vivo are not well defined, leaving a gap in our understanding of the development of humoral immune responses. Here, using an in vivo T cell independent B cell differentiation model, we define a cellular division-dependent cis-regulatory element road map using ATAC-seq. Chromatin accessibility changes correlate with gene expression and reveal the reprogramming of transcriptional networks and the genes they regulate at specific cell divisions. A subset of genes in naive B cells display accessible promoters in the absence of transcription and are marked by H3K27me3, an EZH2 catalyzed repressive modification. Such genes encode regulators of cell division and metabolism and include the essential plasma cell transcription factor Blimp-1. Chemical inhibition of EZH2 results in enhanced plasma cell formation, increased expression of the above gene set, and premature expression of Blimp-1 ex vivo. These data provide insights into cell-division coupled epigenetic and transcriptional processes that program plasma cells.The genomic loci associated with B cell differentiation that are subject to transcriptional and epigenetic regulation in vivo are not well defined, leaving a gap in our understanding of the development of humoral immune responses. Here, using an in vivo T cell independent B cell differentiation model, we define a cellular division-dependent cis-regulatory element road map using ATAC-seq. Chromatin accessibility changes correlate with gene expression and reveal the reprogramming of transcriptional networks and the genes they regulate at specific cell divisions. A subset of genes in naive B cells display accessible promoters in the absence of transcription and are marked by H3K27me3, an EZH2 catalyzed repressive modification. Such genes encode regulators of cell division and metabolism and include the essential plasma cell transcription factor Blimp-1. Chemical inhibition of EZH2 results in enhanced plasma cell formation, increased expression of the above gene set, and premature expression of Blimp-1 ex vivo. These data provide insights into cell-division coupled epigenetic and transcriptional processes that program plasma cells.
The genomic loci associated with B cell differentiation that are subject to transcriptional and epigenetic regulation in vivo are not well defined, leaving a gap in our understanding of the development of humoral immune responses. Here, using an in vivo T cell independent B cell differentiation model, we define a cellular division-dependent cis -regulatory element road map using ATAC-seq. Chromatin accessibility changes correlate with gene expression and reveal the reprogramming of transcriptional networks and the genes they regulate at specific cell divisions. A subset of genes in naive B cells display accessible promoters in the absence of transcription and are marked by H3K27me3, an EZH2 catalyzed repressive modification. Such genes encode regulators of cell division and metabolism and include the essential plasma cell transcription factor Blimp-1. Chemical inhibition of EZH2 results in enhanced plasma cell formation, increased expression of the above gene set, and premature expression of Blimp-1 ex vivo. These data provide insights into cell-division coupled epigenetic and transcriptional processes that program plasma cells.
During B cell differentiation, the role of different genomic loci in transcriptional and epigenetic regulation in vivo is not well defined. Here the authors use an in vivo B cell differentiation model to map cellular division-dependent cis-regulatory element road map with ATAC-seq.
ArticleNumber 1698
Author Guo, Muyao
Bally, Alexander P. R.
Barwick, Benjamin G.
Scharer, Christopher D.
Boss, Jeremy M.
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SSID ssj0000391844
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Snippet The genomic loci associated with B cell differentiation that are subject to transcriptional and epigenetic regulation in vivo are not well defined, leaving a...
During B cell differentiation, the role of different genomic loci in transcriptional and epigenetic regulation in vivo is not well defined. Here the authors...
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SubjectTerms 13/31
38/39
45/15
45/91
631/250/2502/2170
631/337/100
64/60
Accessibility
Animals
Cell differentiation
Cell Differentiation - genetics
Cell division
Cell Division - genetics
Cell Line, Tumor
Chromatin
Differentiation (biology)
DNA Methylation - genetics
Enhancer of Zeste Homolog 2 Protein - antagonists & inhibitors
Enhancer of Zeste Homolog 2 Protein - genetics
Enhancer of Zeste Homolog 2 Protein - metabolism
Epigenesis, Genetic - genetics
Epigenetics
Gene expression
Gene regulation
Genes
Histones - metabolism
Humanities and Social Sciences
Immune response (humoral)
Immunity, Humoral - genetics
Kinases
Lymphocytes B
Lymphocytes T
Metabolism
Mice, Inbred C57BL
Mice, Transgenic
multidisciplinary
Plasma
Plasma cells
Plasma Cells - physiology
Positive Regulatory Domain I-Binding Factor 1 - genetics
Positive Regulatory Domain I-Binding Factor 1 - metabolism
Primary Cell Culture
Promoter Regions, Genetic - genetics
Science
Science (multidisciplinary)
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Title Plasma cell differentiation is controlled by multiple cell division-coupled epigenetic programs
URI https://link.springer.com/article/10.1038/s41467-018-04125-8
https://www.ncbi.nlm.nih.gov/pubmed/29703886
https://www.proquest.com/docview/2031705001
https://www.proquest.com/docview/2032406011
https://pubmed.ncbi.nlm.nih.gov/PMC5923265
https://doaj.org/article/ce454525ef924494b954d29152418aee
Volume 9
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