Details

Autor(en) / Beteiligte

• Zhang, Yu
• McCord, Rachel Patton
• Ho, Yu-Jui
• Lajoie, Bryan R.
• Hildebrand, Dominic G.
• Simon, Aline C.
• Becker, Michael S.
• Alt, Frederick W.
• Dekker, Job

Titel

Spatial Organization of the Mouse Genome and Its Role in Recurrent Chromosomal Translocations

Ist Teil von

• Cell, 2012-03, Vol.148 (5), p.908-921

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2012

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. [Display omitted] ► A high-resolution Hi-C spatial organization map of the G1-arrested mouse cell genome ► Genomic spatial heterogeneity contributes to recurrent chromosomal translocations ► Spatial organization of chromosomes promotes dominant translocations in cis ► Translocations are guided genome-wide by pre-existing spatial genome organization The first high-resolution Hi-C map of the murine G1 nucleus combined with high-throughput genome-wide translocation sequencing reveals how chromatin spatial organization contributes to DSB-driven translocations.