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Series GSE118794 Query DataSets for GSE118794
Status Public on Oct 04, 2018
Title The Chromatin Reader ZMYND8 Regulates Igh Enhancers to Promote Immunoglobulin Class Switch Recombination
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Class Switch Recombination (CSR) is a DNA recombination reaction that diversifies the effector component of antibody responses. CSR is initiated by activation-induced cytidine deaminase (AID), which targets transcriptionally active immunoglobulin heavy chain (Igh) switch donor and acceptor DNA. The 3’ Igh super-enhancer, 3’ Regulatory Region (3’RR), is essential for acceptor region transcription, but how this function is regulated is unknown. Here we identify the chromatin reader ZMYND8 as an essential regulator of the 3’RR and CSR. In B cells, ZMYND8 binds promoters and super-enhancers, including the 3’RR, and controls its activity by modulating the enhancer transcriptional status. In its absence, there is increased 3’RR polymerase loading, and decreased acceptor region transcription and CSR. In addition to CSR, ZMYND8 deficiency impairs somatic hypermutation (SHM) of Igh, which is also dependent on the 3’RR. Thus ZMYND8 controls Igh diversification in mature B lymphocytes by regulating the activity of the 3’ Igh super-enhancer.
Overall design ChIP-seq, RNA-seq and GRO-Seq of wildtype or ZMYND8 KO CH12 or primary B cells.
Contributor(s) Delgado-Benito V, Rosen DB, Wang Q, Gazumyan A, Pai J, Oliveira TY, Sundaravinayagam D, Zhang W, Andreani M, Keller L, Kieffer-Kwon K, Pekowska A, Jung S, Driesner M, Subbotin RI, Casellas R, Chait BT, Nussenzweig MC, Di Virgilio M
Citation(s) 30293785
Submission date Aug 20, 2018
Last update date Mar 25, 2019
Contact name Thiago Y Oliveira
Organization name The Rockefeller University
Department Immunology, Virology and Microbiology
Lab Laboratory of Molecular Immunology
Street address 1230 YORK AVE
State/province New York
ZIP/Postal code 10065
Country USA
Platforms (2)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (44)
GSM3347705 Pol II ChIP-Seq in CH12 - WT, activated rep1
GSM3347706 Pol II ChIP-Seq in CH12 - Rif1–KO, activated
GSM3347707 Pol II ChIP-Seq in CH12 - ZMYND8 KO, activated
BioProject PRJNA486811
SRA SRP158419

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SOFT formatted family file(s) SOFTHelp
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Supplementary file Size Download File type/resource
GSE118794_IgH_germline_regions.fasta.gz 2.4 Kb (ftp)(http) FASTA
GSE118794_RAW.tar 5.5 Gb (http)(custom) TAR (of BIGWIG, BW, TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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