TAD disruption as oncogenic driver
Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology
Cancer Biology | Developmental Biology | Genetics | Genomics | Systems Biology
Topologically Associating Domains (TADs) are conserved during evolution and play roles in guiding and constraining long-range regulation of gene expression. Disruption of TAD boundaries results in aberrant gene expression by exposing genes to inappropriate regulatory elements. Recent studies have shown that TAD disruption is often found in cancer cells and contributes to oncogenesis through two mechanisms. One mechanism locally disrupts domains by deleting or mutating a TAD boundary leading to fusion of the two adjacent TADs. The other mechanism involves genomic rearrangements that break up TADs and creates new ones without directly affecting TAD boundaries. Understanding the mechanisms by which TADs form and control long-range chromatin interactions will therefore not only provide insights into the mechanism of gene regulation in general, but will also reveal how genomic rearrangements and mutations in cancer genomes can lead to misregulation of oncogenes and tumor suppressors.
DOI of Published Version
Curr Opin Genet Dev. 2016 Feb;36:34-40. doi: 10.1016/j.gde.2016.03.008. Epub 2016 Apr 22. Link to article on publisher's site
Current opinion in genetics and development
Valton, Anne-Laure and Dekker, Job, "TAD disruption as oncogenic driver" (2016). Program in Systems Biology Publications and Presentations. 92.