Effect of Zbtb24-depletion on gene expressions during the activation of total splenic B cells
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ABSTRACT:
PROVIDER: PRJNA1009805 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25763978.fastq.gz | Fastqsanger.gz | |||
| SRR25763979.fastq.gz | Fastqsanger.gz | |||
| SRR25763980.fastq.gz | Fastqsanger.gz | |||
| SRR25763981.fastq.gz | Fastqsanger.gz | |||
| SRR25763982.fastq.gz | Fastqsanger.gz |
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Project description:ZBTB24-null ICF2 patients suffer from recurrent infections associated with antibody defects, implying a pivitol role of ZBTB24 in B cell biology. We thus generated B-cell specific Zbtb24 knockout mice and investigated its intrinsic role in B cell development and function both in vitro and in vivo. In accordance with findings obtained in ICF2 patients, Zbtb24 is dispensable for B cell developent and maintenance in mice. Strikingly, lack of Zbtb24 does not significantly compromise the primary & secondary antibody responses against TD-Ags, but reduced TID-Ags-elicited antibodies in vivo. At the cellular level, we discovered that Zbtb24-depletion specifically impaires the plasma cell (PC) differentiation of B1, but not the conventional B2 cells comprising follicular and marginal zone B cells, without impacting their survival and proliferation. Mechanistically, ablation of Zbtb24 suppresses the biosynthesis o heme in B1 cells, and supplementation of hemin largely abrogates the differentiation defects of zbtb24-null B1 cells in vitro. Our study not only provides a plausible explanation for the recurrent respiratory and gastrointestinal infections in ICF2 patients, but is also relevant for other B1 cell-mediated barrier defenses and immune regulations.
2024-09-11 | GSE241746 | GEO
Project description:ZBTB24-null ICF2 patients suffer from recurrent infections associated with antibody defects, implying a pivitol role of ZBTB24 in B cell biology. We thus generated B-cell specific Zbtb24 knockout mice and investigated its intrinsic role in B cell development and function both in vitro and in vivo. In accordance with findings obtained in ICF2 patients, Zbtb24 is dispensable for B cell developent and maintenance in mice. Strikingly, lack of Zbtb24 does not significantly compromise the primary & secondary antibody responses against TD-Ags, but reduced TID-Ags-elicited antibodies in vivo. At the cellular level, we discovered that Zbtb24-depletion specifically impaires the plasma cell (PC) differentiation of B1, but not the conventional B2 cells comprising follicular and marginal zone B cells, without impacting their survival and proliferation. Mechanistically, ablation of Zbtb24 suppresses the biosynthesis o heme in B1 cells, and supplementation of hemin largely abrogates the differentiation defects of zbtb24-null B1 cells in vitro. Our study not only provides a plausible explanation for the recurrent respiratory and gastrointestinal infections in ICF2 patients, but is also relevant for other B1 cell-mediated barrier defenses and immune regulations.
2024-09-11 | GSE241747 | GEO
Project description:We knocked down ZBTB24 expressions in Jurkat cells by lentiviral infections. Four-five days later, virus infected cells (GFP+) were FACS purified for RNA extraction with the Total RNA Kit II (OMEGA). Library construction and sequencing was performed on a BGISEQ-500 by Beijing Genomics Institution (BGI) in Wuhan, China.
2019-05-05 | GSE122191 | GEO
Project description:Effect of Zbtb24-depletion on gene expressions during the activation of peritoneal B1 cells
| PRJNA1009804 | ENA
Project description:Transcriptome analysis in Jurkat cell with sufficient and deficient ZBTB24 expressions
| PRJNA503897 | ENA
Project description:ICF syndrome, a rare autosomal recessive disorder characterized by immunodeficiency, centromeric instability and facial anomalies, is caused by mutations in DNMT3B, ZBTB24, CDCA7 or HELLS. In this study we show that mice deficient for Zbtb24 in the hematopoietic lineage exhibit a phenotype that recapitulates major clinical features of ICF patients, including hypogammaglobulinemia. RNA-Seq analysis of splenic follicular B cells and marginal zone B cells identifies dozens of genes that show differential expression in the absence of Zbtb24. These include Cdca7, Taf6, Cdc40, Ostc, Crisp3 and Il5ra.
2021-10-16 | GSE184699 | GEO
Project description:ZBTB24, encoding a protein of the ZBTB family of transcriptional regulators, is one of four known genes – the other three being DNMT3B, CDCA7 and HELLS – that are mutated in immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome, a genetic disorder characterized by DNA hypomethylation and antibody deficiency. The molecular mechanisms by which ZBTB24 regulates gene expression and the biological functions of ZBTB24 are poorly understood. Here we identified a 12-bp consensus sequence [CT(G/T)CCAGGACCT] occupied by ZBTB24 in the mouse genome. The sequence is present at multiple loci, including the Cdca7 promoter region, and ZBTB24 binding is mostly associated with gene activation. Crystallography and DNA-binding data revealed that the last four of the eight zinc fingers (ZFs) (i.e. ZF5-8) in ZBTB24 confer specificity of DNA binding. Two ICF missense mutations have been identified in the ZBTB24 ZF domain that alter zinc-binding cysteine residues. We demonstrated that the corresponding C382Y and C407G mutations in mouse ZBTB24 abolish specific DNA binding and fail to induce Cdca7 expression. Our analyses indicate, and suggest a structural basis for, the sequence specific recognition by a transcription factor centrally important for the pathogenesis of ICF syndrome.
2019-06-11 | GSE120969 | GEO
Project description:The interplay between transcription factors and epigenetic writers like the DNA methyltransferases (DNMTs), and the role of this interplay in modulating gene expression, is being increasingly appreciated. We investigated the interplay between ZBTB24, a zinc-finger protein belonging to the BTB-POZ family of transcription factors, and the de novo DNA methyltransferase DNMT3B. Both factors, when mutated, cause Immunodeficiency, Centromere Instability, and Facial anomalies (ICF) syndrome, suggesting they are mechanistically linked in some way, but almost nothing is known about ZBTB24. In this study, we identified genomic targets regulated by ZBTB24, and identified its recognition motif, binding to which leads to activation. Chromatin immunoprecipitation in model cell line systems revealed common genes bound by ZBTB24 and DNMT3B, where they function to regulate gene body methylation. Genes coordinately regulated by ZBTB24 and DNMT3B are enriched for molecular mechanisms essential for cellular homeostasis, highlighting the importance of the ZBTB24-DNMT3B interplay in maintaining epigenetic patterns required for normal cellular function.
2018-07-31 | GSE111681 | GEO
Project description:The autosomal recessive immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome is a genetically heterogeneous disorder. Despite recent successes in the identification of the underlying gene defects, it is currently unclear how mutations in any of the four known ICF genes cause a primary immunodeficiency. Here we demonstrate that loss of ZBTB24 in B cells from ICF2 patients impairs non-homologous end-joining (NHEJ) during immunoglobulin class-switch recombination and consequently impairs immunoglobulin production and subtype balance. Mechanistically, we found that ZBTB24 associates with poly(ADP-ribose) polymerase 1 (PARP1) and stimulates auto-poly(ADP-ribosyl)ation of this enzyme. The zinc finger in ZBTB24 binds PARP1-associated poly(ADP-ribose) chains and mediates the PARP1-dependent recruitment of ZBTB24 to DNA breaks. Moreover, by binding to poly(ADP-ribose) chains ZBTB24 protects these moieties from degradation by poly(ADP-ribose) glycohydrolase (PARG). This enhances the poly(ADP-ribose)-dependent interaction between PARP1 and the LIG4/XRCC4 NHEJ complex and promotes NHEJ by facilitating the assembly of this repair complex at DNA breaks. Thus, we uncover ZBTB24 as a regulator of PARP1-dependent NHEJ and class-switch recombination, providing a molecular basis for the immunodeficiency in ICF syndrome.
2020-08-19 | PXD014741 | Pride
Project description:The interplay between transcription factors and epigenetic writers like the DNA methyltransferases (DNMTs), and the role of this interplay in modulating gene expression, is being increasingly appreciated. We investigated the interplay between ZBTB24, a zinc-finger protein belonging to the BTB-POZ family of transcription factors, and the de novo DNA methyltransferase DNMT3B. Both factors, when mutated, cause Immunodeficiency, Centromere Instability, and Facial anomalies (ICF) syndrome, suggesting they are mechanistically linked in some way, but almost nothing is known about ZBTB24. In this study, we identified genomic targets regulated by ZBTB24, and identified its recognition motif, binding to which leads to activation. Chromatin immunoprecipitation in model cell line systems revealed common genes bound by ZBTB24 and DNMT3B, where they function to regulate gene body methylation. Genes coordinately regulated by ZBTB24 and DNMT3B are enriched for molecular mechanisms essential for cellular homeostasis, highlighting the importance of the ZBTB24-DNMT3B interplay in maintaining epigenetic patterns required for normal cellular function.
2018-08-01 | GSE111683 | GEO