Genomics

Dataset Information

0

RAG1 targeting in the genome is dominated by chromatin interactions mediated by the non-core regions of RAG1 and RAG2


ABSTRACT: 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.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE84052 | GEO | 2016/07/06

SECONDARY ACCESSION(S): PRJNA327870

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2016-07-06 | E-GEOD-84052 | biostudies-arrayexpress
2010-04-19 | E-GEOD-21207 | biostudies-arrayexpress
2024-07-05 | GSE250441 | GEO
2015-02-25 | E-GEOD-66248 | biostudies-arrayexpress
2015-02-25 | GSE66248 | GEO
2010-04-20 | GSE21207 | GEO
2015-08-06 | E-GEOD-69475 | biostudies-arrayexpress
2023-07-20 | PXD027151 | Pride
| PRJNA327870 | ENA
2009-01-05 | GSE12655 | GEO