title: Can genome engineering be used to target cancer-associated enhancers?
abstract: 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.
authors.affiliation: Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9601, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Grimmer
authors.forename: Peggy J
authors.initials: PJ
authors.lastname: Farnham
mesh_terms: D000818:Animals; D001665:Binding Sites; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D005818:Genetic Engineering; D023281:Genomics / Q000379:methods; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D011485:Protein Binding; D012045:Regulatory Sequences, Nucleic Acid
keywords: CRISPRs; DNA methylation; TALENs; ZFNs; enhancers; epigenetic therapy; gene expression; genome engineering; genomic nuclease; histone modifications