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Series GSE84052 Query DataSets for GSE84052
Status Public on Jul 06, 2016
Title RAG1 targeting in the genome is dominated by chromatin interactions mediated by the non-core regions of RAG1 and RAG2
Organisms Homo sapiens; Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary The RAG1/RAG2 endonuclease initiates V(D)J recombination at antigen receptor loci but also binds to thousands of places outside of these loci. RAG2 localizes directly to lysine 4 trimethylated histone 3 (H3K4me3) through a PHD finger. The relative contribution of RAG2-dependent and RAG1-intrinsic mechanisms in determining RAG1 binding patterns is not known. Through analysis of deep RAG1 ChIP-seq data, we provide a quantitative description of the forces underlying genome-wide targeting of RAG1. Surprisingly, sequence-specific DNA binding contributes minimally to RAG1 targeting outside of antigen receptor loci. Instead, RAG1 binding is driven by two distinct modes of interaction with chromatin: the first is driven by H3K4me3, promoter-focused, and dependent on the RAG2 PHD, and the second is defined by H3K27Ac, enhancer-focused, and dependent on "non-core" portions of RAG1. Based on this and additional chromatin and genomic features, we formulated a predictive model of RAG1 targeting to the genome. RAG1 binding sites predicted by our model correlate well with observed patterns of RAG1-mediated breaks in human pro-B acute lymphoblastic leukemia. Overall, this study provides an integrative model for RAG1 genome-wide binding and off-target activity, and reveals a novel role for the RAG1 non-core region in RAG1 targeting.
Overall design ChIP-seq profiles of RAG1 from mouse thymocytes, and H3K27Ac from human REH cell line
Contributor(s) Maman Y, Teng G, Seth R, Kleinstein S, Schatz D
Citation(s) 27436288
Submission date Jul 05, 2016
Last update date May 15, 2019
Contact name Yaakov Maman
Organization name Bar-Ilan University
Department Azrieli Faculty of Medicine
Lab Genome Instability & Cancer
Street address Henrietta Szold 8
City Safed
ZIP/Postal code 1311502
Country Israel
Platforms (2)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (4)
GSM2226524 Thy_mm_RAG1_ChIPseq_rep1
GSM2226525 Thy_mm_RAG1_ChIPseq_rep2
GSM2226526 REH_H3K27Ac_ChIPseq
BioProject PRJNA327870
SRA SRP077929

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Supplementary file Size Download File type/resource
GSE84052_RAW.tar 101.6 Mb (http)(custom) TAR (of WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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