The role of enhancers in cancer

被引:297
作者
Sur, Inderpreet [1 ,2 ]
Taipale, Jussi [1 ,2 ,3 ]
机构
[1] Karolinska Inst, Div Funct Genom & Syst Biol, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden
[2] Karolinska Inst, Dept Biosci & Nutr, SE-17177 Stockholm, Sweden
[3] Univ Helsinki, Biomedicum, Genome Scale Biol Program, POB 63, FIN-00014 Helsinki, Finland
关键词
GENOME-WIDE ASSOCIATION; TERT PROMOTER MUTATIONS; HISTONE DEACETYLASE INHIBITOR; TRANSCRIPTION-FACTOR-BINDING; CHRONIC LYMPHOCYTIC-LEUKEMIA; PROTEIN-DNA INTERACTIONS; ACUTE MYELOID-LEUKEMIA; LONG-RANGE INTERACTION; CELL IDENTITY GENES; C-MYC ONCOGENE;
D O I
10.1038/nrc.2016.62
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Enhancer elements function as the logic gates of the genetic regulatory circuitry. One of their most important functions is the integration of extracellular signals with intracellular cell fate information to generate cell type-specific transcriptional responses. Mutations occurring in cancer often misregulate enhancers that normally control the signal-dependent expression of growth-related genes. This misregulation can result from trans-acting mechanisms, such as activation of the transcription factors or epigenetic regulators that control enhancer activity, or can be caused in cis by direct mutations that alter the activity of the enhancer or its target gene specificity. These processes can generate tumour type-specific super-enhancers and establish a 'locked' gene regulatory state that drives the uncontrolled proliferation of cancer cells. Here, we review the role of enhancers in cancer, and their potential as therapeutic targets.
引用
收藏
页码:483 / 493
页数:11
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