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Histone modifications predispose genome regions to breakage and translocation.


ABSTRACT: Chromosome translocations are well-established hallmarks of cancer cells and often occur at nonrandom sites in the genome. The molecular features that define recurrent chromosome breakpoints are largely unknown. Using a combination of bioinformatics, biochemical analysis, and cell-based assays, we identify here specific histone modifications as facilitators of chromosome breakage and translocations. We show enrichment of several histone modifications over clinically relevant translocation-prone genome regions. Experimental modulation of histone marks sensitizes genome regions to breakage by endonuclease challenge or irradiation and promotes formation of chromosome translocations of endogenous gene loci. Our results demonstrate that histone modifications predispose genome regions to chromosome breakage and translocations.

SUBMITTER: Burman B 

PROVIDER: S-EPMC4511214 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Histone modifications predispose genome regions to breakage and translocation.

Burman Bharat B   Zhang Zhuzhu Z ZZ   Pegoraro Gianluca G   Lieb Jason D JD   Misteli Tom T  

Genes & development 20150623 13


Chromosome translocations are well-established hallmarks of cancer cells and often occur at nonrandom sites in the genome. The molecular features that define recurrent chromosome breakpoints are largely unknown. Using a combination of bioinformatics, biochemical analysis, and cell-based assays, we identify here specific histone modifications as facilitators of chromosome breakage and translocations. We show enrichment of several histone modifications over clinically relevant translocation-prone  ...[more]

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