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The RNA binding protein Bcas2 is necessary for antibody class switch in mammalian genomes

ABSTRACT: The RNA binding protein Bcas2 is necessary for antibody class switch in mammalian genomes

PROVIDER: PRJNA1131328 | ENA |

REPOSITORIES: ENA

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The RNA binding protein Bcas2 is necessary for antibody class switch in mammalian genomes

Project description:In children, hyper-IgM syndrome type 1 (HIGM1) is a type of severe antibody disorder, the pathogenesis of which remains unclear. Here we report for the first time that breast cancer amplified sequence 2 (BCAS2), known as an RNA-binding protein, regulates the antibody class transition processes through alternative splicing (AS). Based on integrated analysis of the whole genome sequence and CLIP-seq data, we revealed that BCAS2 regulates AS through binding to the GAAGAA motif of target genes in B cells. Besides, BCAS2 can interact with SRSF7/DHX15 proteins and form spliceosomes that regulates AS and mRNA levels of target genes. In HIGM2 patients, BCAS2 affected the AS and expression of key target genes, and consequently the serum antibody levels. Collectively, the results in this study show that Bcas2 forms a complex with factors such as SRSF7 to regulate AS of key genes, thereby affecting the antibody production. The deletion or reduced expression of BCAS2 may lead to the HIGM2 phenotype. The present study reveals for the first time the pathogenesis of HIGM2, providing a potential molecular target for treatment of the disease.

2025-07-02 | GSE271398 | GEO

Stag2-mediated chromatin dynamics regulates antibody class switch recombination

Project description:Stag2-mediated chromatin dynamics regulates antibody class switch recombination

| PRJNA1372695 | ENA

BCAS2 regulates granulosa cell survival via participating in Flt3l mRNA splicing

Project description:Granulosa cell proliferation and differentiation are essential for follicle development. Breast cancer amplified sequence 2 (BCAS2) is necessary for spermatogenesis, oocyte development, and maintaining the genome integrity of early embryos in mice. However, the function of BCAS2 in granulosa cells is still unknown. We show that conditional disruption of BCAS2 causes follicles development failure; cell proliferation markers PCNA and Ki67 positive cell ratio are unchanged in granulosa cells. However, specific deletion of BCAS2 causes BrdU positive cell ratio to decrease, cell cycle arrest appearance, DNA damage, and cell apoptosis increase in granulosa cells, RPA1 was abnormally stained in granulosa cells. Furthermore, RNA-Seq results reveal that knockout of BCAS2 results in cellular senescence gene unusual expression. BCAS2 participates in the PRP19 complex to mediate alternative splicing (AS) of E2f3 and Flt3l mRNA to inhibit the cell cycle. Knock down of BCAS2 results in a significantly decrease of BrdU positive cell ratio in Human granulosa-like tumor(KGN) cell line. Thus, BCAS2 regulates granulosa cell proliferation, DNA damage repair, and cell apoptosis. BCAS2 is vital for female fertility.

2023-06-01 | GSE218919 | GEO

Stag2-mediated chromatin dynamics regulates antibody class switch recombination [PRO-Seq]

Project description:Stag2-mediated chromatin dynamics regulates antibody class switch recombination [PRO-Seq]

| PRJNA1372707 | ENA

Stag2-mediated chromatin dynamics regulates antibody class switch recombination [3C-HTGTS]

Project description:Stag2-mediated chromatin dynamics regulates antibody class switch recombination [3C-HTGTS]

| PRJNA1372699 | ENA

Stag2-mediated chromatin dynamics regulates antibody class switch recombination [RNA-Seq]

Project description:Stag2-mediated chromatin dynamics regulates antibody class switch recombination [RNA-Seq]

| PRJNA1372706 | ENA

Stag2-mediated chromatin dynamics regulates antibody class switch recombination [ChIP-Seq]

Project description:Stag2-mediated chromatin dynamics regulates antibody class switch recombination [ChIP-Seq]

| PRJNA1372704 | ENA

BATF regulates the expression of Nfil3, Wnt10a and miR155hg for efficient induction of antibody class switch recombination

Project description:BATF functions in both T cells and B cells to control the host response to antigen and promote the production of class switched immunoglobulins. In this study, we demonstrate that BATF expression is increased rapidly, and transiently, immediately following B cell stimulation and use an inducible model of BATF deletion to show that this induction is necessary, and sufficient, to trigger the program of immunoglobulin class switch recombination (CSR). We identify two genes (Nfil3 and miR155gh) that are positively regulated and one gene (Wnt10a) that is negatively regulated by BATF during CSR. All three of these BATF targets play an essential role in CSR and each impacts the expression and/or function of the others. Our observations allow for the positioning of these targets in a network downstream of BATF induction and upstream of the transcriptional activation of Aicda – the gene encoding the enzyme responsible for immunoglobulin gene rearrangements. This work extends the knowledge of the molecular control of CSR and, importantly, positions the induction and function of BATF as an early event in this process.

2018-10-27 | GSE106427 | GEO

Stag2-mediated chromatin dynamics regulates antibody class switch recombination [CSR-HTGTS-Seq]

Project description:Stag2-mediated chromatin dynamics regulates antibody class switch recombination [CSR-HTGTS-Seq]

| PRJNA1372701 | ENA

YY1 Controls Em-3â??RR DNA Loop Formation and Immunoglobulin Heavy Chain Class Switch Recombination.

Project description:Activation of splenic B cells induces formation of a 220kb DNA loop between Em and 3â??RR enhancers in the immunoglobulin heavy chain locus (IgH). This DNA loop has been proposed to be necessary for the crucial immune diversification mechanism of IgH class switch recombination, but the factors that control its formation are unknown. We show that conditional deletion of transcription factor YY1 in primary splenic B cells results in a dramatic drop in formation of this DNA loop, as well as immunoglobulin class switch recombination. Reconstitution of YY1-deleted splenic B cells with various YY1 mutants showed that the C-terminal half of YY1 lacking the transactivation domain restored both Em-3â??RR DNA loop formation as well as class switch recombination. RNA transcript analyses of YY1 conditional deleted splenic B cells suggest that YY1 does not regulate genes needed for DNA looping or CSR. Our results argue for a direct physical mechanism of YY1 mediating long-distance DNA loops and provide strong evidence of the importance of this DNA loop for class switching. Our results provide foundational mechanistic insight into a crucial immune function. Follicular B cells were isolated from the spleens of three C57Bl/6 yy1 fl/fl mice. For each spleen, half the cells received mock treatment and half received TATCRE. The 6 samples were then grown in RPMI medium along with LPS, Il4, OPI, and 20% FBS for 72 hours. The 6 groups of cells were lysed and RNA was isolated for library preparation. Expression differences between Mock and TATCRE treated cells were determined to understand the role of yy1 in B cell class switching.

2016-08-06 | E-GEOD-85259 | biostudies-arrayexpress

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