GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE62063 Query DataSets for GSE62063
Status Public on Dec 04, 2014
Title B cell super-enhancers and regulatory clusters recruit AID tumorigenic activity
Organisms Homo sapiens; Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary The antibody gene mutator AID promiscuously damages oncogenes and B cell identity genes leading to chromosomal translocations and tumorigenesis. Why non-immunoglobulin loci are susceptible to AID activity is unknown. Here we study AID-mediated lesions in the context of nuclear architecture and the B cell regulome. We show that AID targets are not randomly distributed across the genome, but are predominantly clustered within super-enhancers. Unexpectedly, in these domains AID deaminates highly active promoters and eRNA+ enhancers interconnected in some instances over megabases of linear chromatin. Using genome editing we demonstrate that 3D-linked targets cooperate to recruit AID-mediated breaks. Furthermore, a comparison of hypermutation in mouse B cells, AID-induced kataegis in human lymphomas, and translocations in MEFs reveals that AID damages different genes in different cell types. Yet, in all cases, the targets are predominantly associated with topological complex, highly transcribed super-enhancers, demonstrating that these compartments are key mediators of AID recruitment.
Overall design Examination of AID activity in human cells via Single Nucleotide Variant discovery in H3K4me3 ChIP-seq data from 26 MSH2-/-; AIDtg; UGItg, 18 AICDA-/- and 2 unmodified RAMOS clonal populations. Examination of PolII mediated long-range interactions via Chia-PET of RAMOS cells (2 sample). Identification of super-enhancers from H3K27Ac ChIP-Seq data from activated B cells (3 replicates and 1 input control) and RAMOS cells (1 sample and 1 input control), 2 preparations of naive and 2 of germinal center (GC) B cells from human tonsilectomy samples. Mapping of regulatory elements in RAMOS based on H3K4me1 (1 sample) and Nipbl (2 replicates) ChIP-Seq. RNA expression analyses of activated B cells from 3 WT and 3 Il4raU/U mice and RAMOS cells (3 replicates). Mapping of long-range interactions by 4C in activated B cells from a WT and an Il4raU/U mouse with the IL4ra and Il21r locus, respectively, as a viewpoint. Mapping of Super-Enhancers in activated B cells from Il4raU/U and WT control mice (2 samples).
Contributor(s) Qian J, Wang Q, Dose M, Pruett N, Kieffer-Kwon K, Resch W, Liang G, Tang Z, Mathe E, Benner C, Dubois W, Nelson S, Vian L, Oliveira TY, Jankovic M, Hakim O, Gazumyan A, Pavri R, Awasthi P, Song B, Liu G, Chen L, Zhu S, Feigenbaum L, Staudt L, Murre C, Ruan Y, Robbiani DF, Pan-Hammarstrom Q, Nussenzweig MC, Casellas R
Citation(s) 25483777
Submission date Oct 06, 2014
Last update date May 15, 2019
Contact name Marei Dose
Organization name National Institutes of Health
Street address 9000 Rockville Pk
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (4)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (76)
GSM1519128 H3K27Ac_aB_rep1
GSM1519129 H3K27Ac_aB_rep2
GSM1519130 H3K27Ac_aB_rep3
BioProject PRJNA263144
SRA SRP048660

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE62063_AIDmm.SNPs.bed.gz 13.3 Kb (ftp)(http) BED
GSE62063_AIDtgMSH2mmUgi.SNPs.bed.gz 65.0 Kb (ftp)(http) BED
GSE62063_Hotspots.AIDtgMSH2mmUgi.bed.gz 1.5 Kb (ftp)(http) BED
GSE62063_RAMOS.SNPs.bed.gz 153.7 Kb (ftp)(http) BED
GSE62063_RAMOS_H3K27Ac_SuperEnhancers.bed.gz 13.3 Kb (ftp)(http) BED
GSE62063_RAMOS_H3K4me3.peaks.bed.gz 503.0 Kb (ftp)(http) BED
GSE62063_RAMOS_H3K4me3.wig.gz 29.1 Mb (ftp)(http) WIG
GSE62063_RAMOS_RE.bed.gz 963.7 Kb (ftp)(http) BED
GSE62063_RAMOS_RNAPol2_ChiaPET.bed.gz 296.9 Kb (ftp)(http) BED
GSE62063_RAMOS_tonsil_B_SuperEnhancers.bed.gz 30.4 Kb (ftp)(http) BED
GSE62063_RAW.tar 1.1 Gb (http)(custom) TAR (of BED, BW, TAB) 17.0 Mb (ftp)(http) BW
GSE62063_aB_H3K27Ac_SuperEnhancers.bed.gz 17.7 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

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap