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Series GSE136959 Query DataSets for GSE136959
Status Public on Oct 14, 2020
Title A defect in G-quadruplex binding disrupts AID chromatin localization
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary 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.
 
Overall design WT, AID-/- or AID G133V/G133V splenic B cells were stimulated with LPS (30 μg/ml) plus mouse IL-4 (12.5ng/ml) for 72 hours and prepared for ChIP-seq assay.
 
Contributor(s) Lau CM, Chaudhuri J
Citation(s) 33098766
Submission date Sep 05, 2019
Last update date Jan 13, 2021
Contact name Colleen Lau
Organization name Cornell University
Department Microbiology & Immunology
Street address 930 Campus Road
City Ithaca
State/province New York
ZIP/Postal code 14850
Country USA
 
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (12)
GSM4063745 AIDG133V_1
GSM4063746 AIDG133V_2
GSM4063748 AIDG133V_3
Relations
BioProject PRJNA564109
SRA SRP220504

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Supplementary file Size Download File type/resource
GSE136959_RAW.tar 2.8 Gb (http)(custom) TAR (of BW)
GSE136959_pkLstDBanalysis_forGEO.bed.gz 60.8 Kb (ftp)(http) BED
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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