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Plasma cell differentiation is coupled to division-dependent DNA hypomethylation and gene regulation.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE70294 | GEO | 2016/05/01

SECONDARY ACCESSION(S): PRJNA288178

REPOSITORIES: GEO

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Plasma cell differentiation is coupled to division-dependent DNA hypomethylation and gene regulation.

Project description: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.

| S-EPMC5157049 | biostudies-literature

Plasma cell differentiation is coupled to division-dependent DNA hypomethylation and gene regulation.

Project description:Plasma cell differentiation is coupled to division-dependent DNA hypomethylation and gene regulation.

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

Project description: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.

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Dnmt3L-dependent regulation of DNA methylation promotes stem cells differentiation toward primitive germinal cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-09-27 | E-GEOD-44644 | biostudies-arrayexpress

Cell cycle-dependent reconfiguration of the DNA (hydroxy) methylome during terminal differentiation of human B cells into plasma cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-10-30 | E-GEOD-72498 | biostudies-arrayexpress

Marginal zone B cells leverage the Notch2-Myc-mTORC1 signaling axis to achieve division independent plasma cell differentiation.

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-07-22 | GSE180174 | GEO

Dnmt3L-dependent regulation of DNA methylation promotes stem cells differentiation toward primitive germinal cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2013-09-27 | GSE44644 | GEO

IRF4-dependent division-coupled reprogramming events [IRF4cKO.RNAseq]

Project description:To assess the timing and scope of IRF4–dependent reprogramming in vivo, CTV-labeled IRF4–sufficient and –deficient B cells were transferred into mMT hosts. One day later, hosts were challenged with 50 mg LPS. Three days post-LPS challenge, transferred cells were recovered and sorted from divisions 0, 1, 3, 4, 5, and 6 as determined by CTV dilution for RNA–seq.

2021-07-30 | GSE173436 | GEO

IRF4-dependent division-coupled reprogramming events [IRF4cKO.ATACseq]

2021-07-30 | GSE173435 | GEO

Cell cycle-dependent reconfiguration of the DNA (hydroxy) methylome during terminal differentiation of human B cells into plasma cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2015-10-30 | GSE72498 | GEO