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Series GSE62296 Query DataSets for GSE62296
Status Public on Dec 04, 2014
Title Convergent Sense/Antisense Transcription At Intragenic Super-Enhancers Targets AID-initiated Genomic Instability
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Activation-induced cytidine deaminase (AID) initiates both somatic hypermutation (SHM) for antibody affinity maturation and DNA breakage for antibody class switch recombination (CSR) via transcription-dependent cytidine deamination of single stranded DNA targets. While largely specific for immunglobulin genes, AID also acts on a limited set of off-targets, generating oncogenic translocations and mutations that contribute to B cell lymphoma. How AID is recruited to off-targets has been a long-standing mystery. Based on deep GRO-Seq studies of mouse and human B lineage cells activated for CSR or SHM, we report that most robust AID off-target translocations occur within highly focal regions of target genes in which sense and antisense transcription converge. Moreover, we found that such AID-targeting "convergent" transcription arises from antisense transcription that emanates from Super-Enhancers within sense transcribed gene bodies. Our findings provide a mechanistic explanation for AID off-targeting to a small subset of mostly lineage-specific genes in activated B cells.
Overall design We performed GRO-Seq and H3K27Ac ChIP-Seq with different B lineage cell types and MEF cells to find the signatures associated with AID targeting.
Contributor(s) Meng F, Alt FW
Citation(s) 25483776
Submission date Oct 14, 2014
Last update date May 15, 2019
Contact name Feilong Meng
Organization name Boston Children's Hospital
Department PCMM
Lab Fredrick W Alt Lab
Street address 300 Longwood Ave
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
Platforms (3)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (9)
GSM1524919 Naïve_B_GRO-Seq
GSM1524920 GC_B_GRO-Seq
GSM1524921 CSR-Act_B_GRO-Seq
BioProject PRJNA263795
SRA SRP048895

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Supplementary file Size Download File type/resource
GSE62296_RAW.tar 3.1 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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