TiSA: TimeSeriesAnalysis – A pipeline for the analysis of longitudinal transcriptomics data
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE213255 | GEO | 2023/02/13
REPOSITORIES: GEO
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Project description:Changes in DNA methylation are required for the formation of germinal centers (GC), but the mechanisms of such changes are poorly understood. Activation-induced cytidine deaminase (AID) has been recently implicated recently in DNA demethylation through its deaminase activity coupled with DNA repair. We investigated the epigenetic function of AID in vivo in germinal center B cells (GCB) isolated from wild type (WT) and AID-deficient (Aicda-/-) mice. We determined that the transit of B cells through the GC is associated with marked locus-specific loss of methylation and increased methylation diversity, both of which are lost in Aicda-/- animals. Differentially methylated cytosines (DMCs) between GCB and naïve B cells (NB) are enriched in genes that are targeted for somatic hypermutation (SHM) by AID and these genes form networks required for B cell development and proliferation. Finally, we observed significant conservation of AID-dependent epigenetic reprogramming between mouse and human B cells. ERRBS and RNA-seq of wild type and Aicda knockout murine naive and germinal center B cells. ERRBS of human naive and germinal center B cells
2015-09-15 | E-GEOD-71702 | biostudies-arrayexpress
Project description:Changes in DNA methylation are required for the formation of germinal centers (GC), but the mechanisms of such changes are poorly understood. Activation-induced cytidine deaminase (AID) has been recently implicated recently in DNA demethylation through its deaminase activity coupled with DNA repair. We investigated the epigenetic function of AID in vivo in germinal center B cells (GCB) isolated from wild type (WT) and AID-deficient (Aicda-/-) mice. We determined that the transit of B cells through the GC is associated with marked locus-specific loss of methylation and increased methylation diversity, both of which are lost in Aicda-/- animals. Differentially methylated cytosines (DMCs) between GCB and naïve B cells (NB) are enriched in genes that are targeted for somatic hypermutation (SHM) by AID and these genes form networks required for B cell development and proliferation. Finally, we observed significant conservation of AID-dependent epigenetic reprogramming between mouse and human B cells.
2015-09-15 | GSE71702 | GEO
Project description:Activation-induced cytidine deaminase (AID) is essential for the generation of antibody memory but also targets oncogenes among others. We investigated the transcriptional regulation of the AID gene, Aicda, in the class switch–inducible CH12F3-2 cells, and found that the Aicda regulation involves derepression by several layers of positive regulatory elements in addition to the 5’ promoter region. The 5’ upstream region contains functional motifs for the response to signaling by cytokines, CD40-ligand, or stimuli that activate NF-κB. The first intron contains functional binding elements for the ubiquitous silencers c-Myb and E2f and for B cell–specific activator Pax5 and E-box-binding proteins. To confirm involvement of these transcription factors in Acida regulation, we examined their expression profile of these factors in naïve and germinal center B cells.
2009-10-27 | GSE18746 | GEO
Project description:Activation-induced cytidine deaminase (AID) plays a vital role in adaptive immunity by enabling class switch recombination (CSR) and somatic hypermutation (SHM). While many molecular factors affect AID targeting and function, mounting evidence implicates G-quadruplex (G4) nucleic acid structures as critical effectors of AID biology. To examine the function of AID-G4 binding in vivo, we generated a knock-in mouse with a mutation in Aicda (AIDG133V) that disrupts AID-G4 binding without altering DNA deaminase activity. AIDG133V mice completely lack CSR and SHM, modeling the pathology of hyper-IgM syndrome patients with an orthologous mutation. ChIP-sequencing experiments reveal a broad defect in AIDG133V chromatin localization, implicating AID-G4 binding in genome-wide AID targeting. We find that major histocompatibility complex (MHC) class II genes are AID targets, and that increased AID expression in diffuse large B-cell lymphomas (DLBCLs) correlates with decreased MHC class II expression. Given that loss of MHC class II expression in DLBCLs is highly correlated with adverse outcomes, AID-dependent gene regulation may provide a novel therapeutic target.
2020-10-14 | GSE136959 | GEO
Project description:TET enzymes are dioxygenases that promote DNA demethylation by oxidizing the methyl group of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Here we report a close correspondence between 5hmC-marked regions, chromatin accessibility and enhancer activity in B cells, and a strong enrichment for consensus binding motifs for basic region-leucine zipper (bZIP) transcription factors at TET-responsive genomic regions. Functionally, Tet2 and Tet3 regulate class switch recombination (CSR) in murine B cells by enhancing expression of Aicda, encoding the cytidine deaminase AID essential for CSR. TET enzymes deposit 5hmC, demethylate and maintain chromatin accessibility at two TET-responsive elements, TetE1 and TetE2, located within a superenhancer in the Aicda locus. Transcriptional profiling identified BATF as the bZIP transcription factor involved in TET-dependent Aicda expression. 5hmC is not deposited at TetE1 in activated Batf-deficient B cells, indicating that BATF recruits TET proteins to the Aicda enhancer. Our data emphasize the importance of TET enzymes for bolstering AID expression, and highlight 5hmC as an epigenetic mark that captures enhancer dynamics during cell activation.
2019-04-29 | GSE116207 | GEO
Project description:TET enzymes are dioxygenases that promote DNA demethylation by oxidizing the methyl group of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Here we report a close correspondence between 5hmC-marked regions, chromatin accessibility and enhancer activity in B cells, and a strong enrichment for consensus binding motifs for basic region-leucine zipper (bZIP) transcription factors at TET-responsive genomic regions. Functionally, Tet2 and Tet3 regulate class switch recombination (CSR) in murine B cells by enhancing expression of Aicda, encoding the cytidine deaminase AID essential for CSR. TET enzymes deposit 5hmC, demethylate and maintain chromatin accessibility at two TET-responsive elements, TetE1 and TetE2, located within a superenhancer in the Aicda locus. Transcriptional profiling identified BATF as the bZIP transcription factor involved in TET-dependent Aicda expression. 5hmC is not deposited at TetE1 in activated Batf-deficient B cells, indicating that BATF recruits TET proteins to the Aicda enhancer. Our data emphasize the importance of TET enzymes for bolstering AID expression, and highlight 5hmC as an epigenetic mark that captures enhancer dynamics during cell activation.
2019-04-29 | GSE116206 | GEO
Project description:TET enzymes are dioxygenases that promote DNA demethylation by oxidizing the methyl group of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Here we report a close correspondence between 5hmC-marked regions, chromatin accessibility and enhancer activity in B cells, and a strong enrichment for consensus binding motifs for basic region-leucine zipper (bZIP) transcription factors at TET-responsive genomic regions. Functionally, Tet2 and Tet3 regulate class switch recombination (CSR) in murine B cells by enhancing expression of Aicda, encoding the cytidine deaminase AID essential for CSR. TET enzymes deposit 5hmC, demethylate and maintain chromatin accessibility at two TET-responsive elements, TetE1 and TetE2, located within a superenhancer in the Aicda locus. Transcriptional profiling identified BATF as the bZIP transcription factor involved in TET-dependent Aicda expression. 5hmC is not deposited at TetE1 in activated Batf-deficient B cells, indicating that BATF recruits TET proteins to the Aicda enhancer. Our data emphasize the importance of TET enzymes for bolstering AID expression, and highlight 5hmC as an epigenetic mark that captures enhancer dynamics during cell activation.
2019-04-29 | GSE116205 | GEO
Project description:TET enzymes are dioxygenases that promote DNA demethylation by oxidizing the methyl group of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Here we report a close correspondence between 5hmC-marked regions, chromatin accessibility and enhancer activity in B cells, and a strong enrichment for consensus binding motifs for basic region-leucine zipper (bZIP) transcription factors at TET-responsive genomic regions. Functionally, Tet2 and Tet3 regulate class switch recombination (CSR) in murine B cells by enhancing expression of Aicda, encoding the cytidine deaminase AID essential for CSR. TET enzymes deposit 5hmC, demethylate and maintain chromatin accessibility at two TET-responsive elements, TetE1 and TetE2, located within a superenhancer in the Aicda locus. Transcriptional profiling identified BATF as the bZIP transcription factor involved in TET-dependent Aicda expression. 5hmC is not deposited at TetE1 in activated Batf-deficient B cells, indicating that BATF recruits TET proteins to the Aicda enhancer. Our data emphasize the importance of TET enzymes for bolstering AID expression, and highlight 5hmC as an epigenetic mark that captures enhancer dynamics during cell activation.
2019-04-29 | GSE116204 | GEO
Project description:TET enzymes are dioxygenases that promote DNA demethylation by oxidizing the methyl group of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Here we report a close correspondence between 5hmC-marked regions, chromatin accessibility and enhancer activity in B cells, and a strong enrichment for consensus binding motifs for basic region-leucine zipper (bZIP) transcription factors at TET-responsive genomic regions. Functionally, Tet2 and Tet3 regulate class switch recombination (CSR) in murine B cells by enhancing expression of Aicda, encoding the cytidine deaminase AID essential for CSR. TET enzymes deposit 5hmC, demethylate and maintain chromatin accessibility at two TET-responsive elements, TetE1 and TetE2, located within a superenhancer in the Aicda locus. Transcriptional profiling identified BATF as the bZIP transcription factor involved in TET-dependent Aicda expression. 5hmC is not deposited at TetE1 in activated Batf-deficient B cells, indicating that BATF recruits TET proteins to the Aicda enhancer. Our data emphasize the importance of TET enzymes for bolstering AID expression, and highlight 5hmC as an epigenetic mark that captures enhancer dynamics during cell activation.
2019-04-29 | GSE116203 | GEO
Project description:TET enzymes are dioxygenases that promote DNA demethylation by oxidizing the methyl group of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Here we report a close correspondence between 5hmC-marked regions, chromatin accessibility and enhancer activity in B cells, and a strong enrichment for consensus binding motifs for basic region-leucine zipper (bZIP) transcription factors at TET-responsive genomic regions. Functionally, Tet2 and Tet3 regulate class switch recombination (CSR) in murine B cells by enhancing expression of Aicda, encoding the cytidine deaminase AID essential for CSR. TET enzymes deposit 5hmC, demethylate and maintain chromatin accessibility at two TET-responsive elements, TetE1 and TetE2, located within a superenhancer in the Aicda locus. Transcriptional profiling identified BATF as the bZIP transcription factor involved in TET-dependent Aicda expression. 5hmC is not deposited at TetE1 in activated Batf-deficient B cells, indicating that BATF recruits TET proteins to the Aicda enhancer. Our data emphasize the importance of TET enzymes for bolstering AID expression, and highlight 5hmC as an epigenetic mark that captures enhancer dynamics during cell activation.
2019-04-29 | GSE116202 | GEO