B cell activation and plasma cell differentiation are inhibited by de novo DNA methylation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA352270 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4786660_1.fastq.gz | Fastqsanger.gz | |||
| SRR4786660_2.fastq.gz | Fastqsanger.gz | |||
| SRR4786670_1.fastq.gz | Fastqsanger.gz | |||
| SRR4786670_2.fastq.gz | Fastqsanger.gz | |||
| SRR4786680_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 452 |
Similar Datasets
Project description:B cells provide humoral immunity by differentiating into antibody-secreting plasma cells, a process that requires cellular division and is linked to DNA hypomethylation. Conversely, little is known about how de novo deposition of DNA methylation affects B cell fate and function. Here we show that genetic deletion of the de novo DNA methyltransferases Dnmt3a and Dnmt3b (Dnmt3-deficient) in mouse B cells results in normal B cell development and maturation, but increased cell activation and expansion of the germinal center B cell and plasma cell populations upon immunization. Gene expression is mostly unaltered in naive and germinal center B cells, but dysregulated in Dnmt3-deficient plasma cells. Differences in gene expression are proximal to Dnmt3-dependent DNA methylation and chromatin changes, both of which coincide with E2A and PU.1-IRF composite-binding motifs. Thus, de novo DNA methylation limits B cell activation, represses the plasma cell chromatin state, and regulates plasma cell differentiation.
2017-12-31 | GSE89471 | GEO
Project description:B cells provide humoral immunity by differentiating into antibody-secreting plasma cells, a process that requires cell division and is linked to DNA hypomethylation and gene regulation. Conversely, accumulation of DNA methylation in B cell differentiation is less apparent. To determine the role of de novo DNA methylation in B cell differentiation, the de novo DNA methyltransferases, Dnmt3a and Dnmt3b, were deleted in B cells resulting in phenotypically normal B cell development in the bone marrow, spleen and lymph nodes. However, upon immunologic challenge, mice deficient for Dnmt3a and Dnmt3b (Dnmt3-deficient) accumulated more antigen-specific B cells and bone marrow chimeras showed this was cell-autonomous. Additionally, a five-fold increase in splenic and bone marrow plasma cells was observed. Molecular analysis revealed that Dnmt3-deficient bone marrow plasma cells failed to repress gene expression to the same level as their Dnmt3ab-sufficient counterparts. This was coupled with a failure of Dnmt3-deficient germinal center B cells and plasma cells to gain and/or maintain DNA methylation at several thousand loci that were clustered in enhancers of genes that function in B cell activation and homing. Analysis of chromatin accessibility showed Dnmt3-deficient plasma cells had increased accessibility at several genes involved in hematopoiesis and B cell differentiation. These data show that de novo DNA methylation limits B cell activation, proliferation and differentiation, and support a model whereby DNA methylation represses the aberrant transcription of genes silenced in B cell differentiation to maintain plasma cell homeostasis.
2017-12-31 | GSE89467 | GEO
Project description:B cells provide humoral immunity by differentiating into antibody-secreting plasma cells, a process that requires cell division and is linked to DNA hypomethylation and gene regulation. Conversely, accumulation of DNA methylation in B cell differentiation is less apparent. To determine the role of de novo DNA methylation in B cell differentiation, the de novo DNA methyltransferases, Dnmt3a and Dnmt3b, were deleted in B cells resulting in phenotypically normal B cell development in the bone marrow, spleen and lymph nodes. However, upon immunologic challenge, mice deficient for Dnmt3a and Dnmt3b (Dnmt3-deficient) accumulated more antigen-specific B cells and bone marrow chimeras showed this was cell-autonomous. Additionally, a five-fold increase in splenic and bone marrow plasma cells was observed. Molecular analysis revealed that Dnmt3-deficient bone marrow plasma cells failed to repress gene expression to the same level as their Dnmt3ab-sufficient counterparts. This was coupled with a failure of Dnmt3-deficient germinal center B cells and plasma cells to gain and/or maintain DNA methylation at several thousand loci that were clustered in enhancers of genes that function in B cell activation and homing. Analysis of chromatin accessibility showed Dnmt3-deficient plasma cells had increased accessibility at several genes involved in hematopoiesis and B cell differentiation. These data show that de novo DNA methylation limits B cell activation, proliferation and differentiation, and support a model whereby DNA methylation represses the aberrant transcription of genes silenced in B cell differentiation to maintain plasma cell homeostasis.
2017-12-31 | GSE89470 | GEO
Project description:B cells provide humoral immunity by differentiating into antibody-secreting plasma cells, a process that requires cell division and is linked to DNA hypomethylation and gene regulation. Conversely, accumulation of DNA methylation in B cell differentiation is less apparent. To determine the role of de novo DNA methylation in B cell differentiation, the de novo DNA methyltransferases, Dnmt3a and Dnmt3b, were deleted in B cells resulting in phenotypically normal B cell development in the bone marrow, spleen and lymph nodes. However, upon immunologic challenge, mice deficient for Dnmt3a and Dnmt3b (Dnmt3-deficient) accumulated more antigen-specific B cells and bone marrow chimeras showed this was cell-autonomous. Additionally, a five-fold increase in splenic and bone marrow plasma cells was observed. Molecular analysis revealed that Dnmt3-deficient bone marrow plasma cells failed to repress gene expression to the same level as their Dnmt3ab-sufficient counterparts. This was coupled with a failure of Dnmt3-deficient germinal center B cells and plasma cells to gain and/or maintain DNA methylation at several thousand loci that were clustered in enhancers of genes that function in B cell activation and homing. Analysis of chromatin accessibility showed Dnmt3-deficient plasma cells had increased accessibility at several genes involved in hematopoiesis and B cell differentiation. These data show that de novo DNA methylation limits B cell activation, proliferation and differentiation, and support a model whereby DNA methylation represses the aberrant transcription of genes silenced in B cell differentiation to maintain plasma cell homeostasis.
2017-12-31 | GSE89412 | GEO
Project description:De novo Characterization of Cell-free DNA Fragmentation Hotspots in Plasma Whole-genome Sequencing.
| PRJNA881451 | ENA
Project description:De novo Characterization of Cell-free DNA Fragmentation Hotspots in Plasma Whole-genome Sequencing.
| PRJNA881452 | ENA
Project description:Previously, we published a dataset of human blood plasma and serum samples of 10 healthy males and 10 healthy females, fractionated on a set of sorbents (cation exchange Toyopearl CM-650M, CM Bio-Gel A, SP Sephadex C-25 and anion exchange QAE Sephadex A-25) and analyzed by LC-MS/MS individually and pooled in equal amounts (Supplementary Table S1, Sheet 1) [33]. Blood is a complex tissue and can theoretically contain products of all processes occurring in different parts of the body. To identify potential sources of “alien” (non-human) plasma peptides, we performed a de novo analysis of mass spectrometry data. De novo analysis is a less efficient method of identification than search against databases, since the accuracy and resolution of modern mass spectrometers such as QTOF or Orbitrap remains not high enough. However, we use de novo analysis to identify organisms that include the most abundant components of the complex peptide mixture. This procedure allows us to develop a hypothesis and then perform a standard search against a database of proteins of identified organisms. The de novo identification was carried out using PEAKS Studio 8.0 (Bioinformatics Solutions Inc., Canada) and mass spectrometry driven BLAST analysis against the RefSeq non-redundant database NCBInr (https://www.ncbi.nlm.nih.gov/protein/). Mass spectra identified as fragments of proteins from different organisms were assigned to a taxonomic level at which these different organisms converged (Supplementary Table S2). 33. Arapidi, G. et al. Peptidomics dataset: Blood plasma and serum samples of healthy donors fractionated on a set of chromatography sorbents. Data Brief 18, 1204–1211 (2018).
2024-06-14 | PXD027701 | Pride
Project description:HGSVC3 - Verkko De Novo Assemblies
| PRJEB76276 | ENA
Project description:HGSVC3 - hifiasm De Novo Assemblies
| PRJEB83624 | ENA