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| 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
Other
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| 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.
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| Overall design |
ChIP-seq, RNA-seq and GRO-Seq of wildtype or ZMYND8 KO CH12 or primary B cells.
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| 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 |
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| Submission date |
Aug 20, 2018 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Thiago Y Oliveira |
| E-mail(s) |
toliveira@rockefeller.edu
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| Organization name |
The Rockefeller University
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| Department |
Immunology, Virology and Microbiology
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| Lab |
Laboratory of Molecular Immunology
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| Street address |
1230 YORK AVE
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| City |
NEW YORK |
| State/province |
New York |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (2) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (44)
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| 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 |
| GSM3347708 |
Pol II ChIP-Seq in CH12 - ZMYND8 KO, unactivated |
| GSM3347709 |
ZMYND8 ChIP-Seq in CH12 cells – ZMYND8 KO1 |
| GSM3347710 |
ZMYND8 ChIP-Seq in CH12 cells – ZMYND8 KO2 |
| GSM3347711 |
ZMYND8 ChIP-Seq in CH12 cells – WT rep1 |
| GSM3347712 |
ZMYND8 ChIP-Seq in CH12 cells – WT rep2 |
| GSM3347713 |
Pol II ChIP-Seq in primary B cells – Cd19-Cre/+ rep1 |
| GSM3347714 |
Pol II ChIP-Seq in primary B cells – Cd19-Cre/+ rep2 |
| GSM3347715 |
Pol II ChIP-Seq in primary B cells – Cd19-Cre/+ rep3 |
| GSM3347716 |
Pol II ChIP-Seq in primary B cells – ZMYND8-F/F Cd19-Cre/+ rep 1 |
| GSM3347717 |
Pol II ChIP-Seq in primary B cells – ZMYND8-F/F Cd19-Cre/+ rep 2 |
| GSM3347718 |
Pol II ChIP-Seq in primary B cells – ZMYND8-F/F Cd19-Cre/+ rep 3 |
| GSM3347719 |
ZMYND8 ChIP-Seq in primary B cells – Cd19-Cre/+ rep1 |
| GSM3347720 |
ZMYND8 ChIP-Seq in primary B cells – Cd19-Cre/+ rep2 |
| GSM3347721 |
ZMYND8 ChIP-Seq in primary B cells – Cd19-Cre/+ rep3 |
| GSM3347722 |
RNA-Seq in CH12 cells – WT, unactivated rep 1 |
| GSM3347723 |
RNA-Seq in CH12 cells – WT, unactivated rep 2 |
| GSM3347724 |
RNA-Seq in CH12 cells – WT, unactivated rep 3 |
| GSM3347725 |
RNA-Seq in CH12 cells – WT, activated rep1 |
| GSM3347726 |
RNA-Seq in CH12 cells – WT, activated rep2 |
| GSM3347727 |
RNA-Seq in CH12 cells – WT, activated rep3 |
| GSM3347728 |
RNA-Seq in CH12 cells – WT clone, unactivated rep1 |
| GSM3347729 |
RNA-Seq in CH12 cells – WT clone, unactivated rep2 |
| GSM3347730 |
RNA-Seq in CH12 cells – WT clone, unactivated rep3 |
| GSM3347731 |
RNA-Seq in CH12 cells – WT clone, activated rep 1 |
| GSM3347732 |
RNA-Seq in CH12 cells – WT clone, activated rep 2 |
| GSM3347733 |
RNA-Seq in CH12 cells – WT clone, activated rep 3 |
| GSM3347734 |
RNA-Seq in CH12 cells – ZMYND8 KO1 clone, unactivated rep1 |
| GSM3347735 |
RNA-Seq in CH12 cells – ZMYND8 KO1 clone, unactivated rep2 |
| GSM3347736 |
RNA-Seq in CH12 cells – ZMYND8 KO1 clone, unactivated rep3 |
| GSM3347737 |
RNA-Seq in CH12 cells – ZMYND8 KO1 clone, activated rep1 |
| GSM3347738 |
RNA-Seq in CH12 cells – ZMYND8 KO1 clone, activated rep2 |
| GSM3347739 |
RNA-Seq in CH12 cells – ZMYND8 KO1 clone, activated rep3 |
| GSM3347740 |
RNA-Seq in CH12 cells – ZMYND8 KO2 clone, unactivated rep1 |
| GSM3347741 |
RNA-Seq in CH12 cells – ZMYND8 KO2 clone, unactivated rep2 |
| GSM3347742 |
RNA-Seq in CH12 cells – ZMYND8 KO2 clone, unactivated rep3 |
| GSM3347743 |
RNA-Seq in CH12 cells – ZMYND8 KO2 clone, activated rep1 |
| GSM3347744 |
RNA-Seq in CH12 cells – ZMYND8 KO2 clone, activated rep2 |
| GSM3347745 |
RNA-Seq in CH12 cells – ZMYND8 KO2 clone, activated rep3 |
| GSM3347746 |
GRO-Seq in primary B cells – ZMYND8-F/F Cd19-Cre/+ rep 1 |
| GSM3347747 |
GRO-Seq in primary B cells – ZMYND8-F/F Cd19-Cre/+ rep 2 |
| GSM3347748 |
GRO-Seq in primary B cells – ZMYND8-F/F |
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| Relations |
| BioProject |
PRJNA486811 |
| SRA |
SRP158419 |
| 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 Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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