Can genome engineering be used to target cancer-associated enhancers?

被引:0
|
作者
Grimmer, Matthew R. [1 ]
Farnham, Peggy J. [1 ]
机构
[1] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90089 USA
基金
美国国家卫生研究院;
关键词
CRISPRs; DNA methylation; enhancers; epigenetic therapy; gene expression; genome engineering; genomic nuclease; histone modifications; TALENs; ZFNs; RNA-GUIDED ENDONUCLEASES; TRANSCRIPTION FACTORS; DNA METHYLATION; EPIGENETIC MODIFICATIONS; SUPER-ENHANCERS; GENE ACTIVATION; TAL EFFECTORS; MYC ENHANCER; CAS9; SPECIFICITY;
D O I
10.2217/EPI.14.30
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Transcriptional misregulation is involved in the development of many diseases, especially neoplastic transformation. Distal regulatory elements, such as enhancers, play a major role in specifying cell-specific transcription patterns in both normal and diseased tissues, suggesting that enhancers may be prime targets for therapeutic intervention. By focusing on modulating gene regulation mediated by cell type-specific enhancers, there is hope that normal epigenetic patterning in an affected tissue could be restored with fewer side effects than observed with treatments employing relatively nonspecific inhibitors such as epigenetic drugs. New methods employing genomic nucleases and site-specific epigenetic regulators targeted to specific genomic regions, using either artificial DNA-binding proteins or RNA-DNA interactions, may allow precise genome engineering at enhancers. However, this field is still in its infancy and further refinements that increase specificity and efficiency are clearly required.
引用
收藏
页码:493 / 501
页数:9
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