Spatial organization of the mouse genome and its role in recurrent chromosomal translocations
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Authors
Zhang, YuMcCord, Rachel Patton
Ho, Yu-Jui
Lajoie, Bryan R.
Hildebrand, Dominic G.
Simon, Alince C.
Becker, Michael B.
Alt, Frederick W.
Dekker, Job
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyProgram in Systems Biology
Program in Gene Function and Expression
Document Type
Journal ArticlePublication Date
2012-03-02Keywords
AnimalsDNA Breaks, Double-Stranded
G1 Phase
*Genome
High-Throughput Nucleotide Sequencing
Mice
Mice, 129 Strain
Mice, Inbred BALB C
Neoplasms
Precursor Cells, B-Lymphoid
Receptors, Antigen
*Translocation, Genetic
Biochemistry, Biophysics, and Structural Biology
Genetics and Genomics
Systems Biology
Metadata
Show full item recordAbstract
The extent to which the three-dimensional organization of the genome contributes to chromosomal translocations is an important question in cancer genomics. We generated a high-resolution Hi-C spatial organization map of the G1-arrested mouse pro-B cell genome and used high-throughput genome-wide translocation sequencing to map translocations from target DNA double-strand breaks (DSBs) within it. RAG endonuclease-cleaved antigen-receptor loci are dominant translocation partners for target DSBs regardless of genomic position, reflecting high-frequency DSBs at these loci and their colocalization in a fraction of cells. To directly assess spatial proximity contributions, we normalized genomic DSBs via ionizing radiation. Under these conditions, translocations were highly enriched in cis along single chromosomes containing target DSBs and within other chromosomes and subchromosomal domains in a manner directly related to pre-existing spatial proximity. By combining two high-throughput genomic methods in a genetically tractable system, we provide a new lens for viewing cancer genomes.Source
Cell. 2012 Mar 2;148(5):908-21. Epub 2012 Feb 16. Link to article on publisher's siteDOI
10.1016/j.cell.2012.02.002Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49921PubMed ID
22341456Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.cell.2012.02.002