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SRX22079179: GSM7838942: S2_Input_UN_WT; Mus musculus; ChIP-Seq
1 ILLUMINA (Illumina NovaSeq 6000) run: 42.4M spots, 8.6G bases, 2.5Gb downloads

External Id: GSM7838942_r1
Submitted by: Nijnik Lab, Physiology, McGill University
Study: B-cell Intrinsic Regulation of Antibody Mediated Immunity by Histone H2A Deubiquitinase BAP1 [ChIP-seq]
show Abstracthide Abstract
BAP1 is a deubiquitinase (DUB) of the Ubiquitin C-terminal Hydrolase (UCH) family that regulates gene expression and other cellular processes, through its direct catalytic activity on the repressive epigenetic mark histone H2AK119ub, as well as several other substrates. BAP1 is also a highly important tumor suppressor, expressed and functional across many cell types and tissues. In recent work, we demonstrated a cell intrinsic role of BAP1 in the B cell lineage development in murine bone marrow, however the role of BAP1 in the regulation of B cell mediated humoral immune response has not been previously explored. In the current study, we demonstrate that a B-cell intrinsic loss of BAP1 function in activated B cells in the Bap1fl/fl C?1-cre murine model results in a severe defect in antibody production, with altered dynamics of germinal centre B cell, memory B cell, and plasma cell numbers. At the cellular and molecular level, BAP1 was dispensable for B cell immunoglobulin class switching but resulted in an impaired proliferation of activated B cells, with genome-wide dysregulation in histone H2AK119ub levels and gene expression. In summary, our study establishes the B-cell intrinsic role of BAP1 in antibody mediated immune response and indicates its central role in the regulation of the genome-wide landscapes of histone H2AK119ub and downstream transcriptional programs of B cell activation and humoral immunity. Overall design: To identify the genomic regions directly regulated by BAP1 in activated B cells, we conducted ChIP-seq to map the BAP1 genome-wide DNA-binding sites in CH12F3 cells, firstly using wild type cells with an anti-BAP1 antibody, repeating the analyses with both untreated cells and cells at 72 hours of stimulation with TGF-ß, IL-4, and anti-CD40, corresponding to the standard protocol for CH12F3 cell activation. ChIP-seq analysis was further repeated using the CH12F3 cells stably expressing 3xFLAG-tagged BAP1 with an antibody against the FLAG epitope.
Sample: S2_Input_UN_WT
SAMN37798998 • SRS19145886 • All experiments • All runs
Organism: Mus musculus
Library:
Name: GSM7838942
Instrument: Illumina NovaSeq 6000
Strategy: ChIP-Seq
Source: GENOMIC
Selection: ChIP
Layout: PAIRED
Construction protocol: CH12F3 cells were either unstimulated or stimulated with a cocktail consisting of recombinant human TGFβ1 (R&D systems, 240-B, 1 ng/mL), recombinant mouse IL4 (Preprotech, 214-14, 10 ng/mL), and functional grade purified α-mouse CD40 (eBiosciences, 16-0401, 1 ug/mL) for 72 hours to induce IgA class-switching. Cells were fixed with 1% formaldehyde in the culture media for 10 minutes at room temperature, followed by addition of 0.125M of glycine to stop fixation. Nuclei were extracted with 5 minutes lysis in 0.25% Triton buffer, followed by 30 minutes in 200mM NaCl buffer. Nuclei were resuspended in sonication buffer and sonicated for twelve cycles of 30 seconds with a digital sonifier (Branson Ultrasonics) at 80%, with 30 seconds rest in cooled circulating water. Beads immunocomplexes were prepared overnight by conjugating 40μL of Dynabeads Protein G (Invitrogen, Life Technologies) with antibodies: anti-BAP1 (Cell Signaling Technology, D1W9B, 52.8 μg), anti-FLAG M2 (Sigma, F1804, 5 μg) or anti-H2AK119Ub (Cell Signaling Technology, D27C4, 5 μg). Immunoprecipitation was performed by overnight incubation of antibody-bead matrices with sheared chromatin from the equivalent of 5x106 cells. For BAP1-FLAG ChIP, 6 washes were performed with medium-stringency buffers, while 4 low-stringency washes were used for histone ChIP . Samples were de-crosslinked by overnight incubation at 65̊C in 1% SDS buffer. Following RNaseA and Proteinase K enzymatic treatments, ChIP DNA was purified using Qiaquick PCR Cleanup kit (Qiagen). DNA yields and quality were assessed using Bioanalyzer (Agilent). Library preparation were performed using the KAPA HyperPrep Kit. Sequencing was assessed using Novaseq 6000.
Runs: 1 run, 42.4M spots, 8.6G bases, 2.5Gb
Run# of Spots# of BasesSizePublished
SRR2637212142,376,0398.6G2.5Gb2024-02-15

ID:
30009927

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