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

被引：429

作者：

Zhang, Yu ^{[1
,2
,3
]}

McCord, Rachel Patton ^{[4
,5
]}

Ho, Yu-Jui ^{[1
,2
,3
]}

Lajoie, Bryan R. ^{[4
,5
]}

Hildebrand, Dominic G. ^{[1
,2
,3
]}

Simon, Aline C. ^{[1
,2
,3
]}

Becker, Michael S. ^{[1
,2
,3
]}

Alt, Frederick W. ^{[1
,2
,3
]}

Dekker, Job ^{[4
,5
]}

机构：

[1] Childrens Hosp, Program Cellular & Mol Med, Immune Dis Inst, Howard Hughes Med Inst, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA

[4] Univ Massachusetts, Sch Med, Dept Biochem & Mol Biol, Programs Syst Biol, Worcester, MA 01605 USA

[5] Univ Massachusetts, Sch Med, Dept Biochem & Mol Biol, Programs Gene Funct & Express, Worcester, MA 01605 USA

来源：

CELL | 2012年 / 148卷 / 05期

关键词：

DOUBLE-STRAND BREAKS; V(D)J RECOMBINATION; SEQUENCING REVEALS; B-CELLS; C-MYC; MECHANISMS; CANCER; REARRANGEMENTS; LYMPHOCYTES; STABILITY;

D O I：

10.1016/j.cell.2012.02.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：908 / 921

页数：14

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