%0 Journal Article
%T Knocking Out Enhancers to Enhance Epigenetic Research
%J -
%D 2019
%R https://doi.org/10.1016/j.tig.2018.10.001
%X Advances in epigenetics have uncovered a myriad of transcription factor binding sites and chromatin modifications in presumed DNA control elements that regulate gene activation (enhancers) or repression (silencers). Identification of enhancers has relied extensively on the production of animals carrying enhancer reporter transgenes; however, recent studies reporting knockouts of such presumed enhancers have described many cases in which the enhancer is nonessential [ 1 Will A.J. et al. Composition and dosage of a multipartite enhancer cluster control developmental expression of Ihh (Indian hedgehog). Nat. Genet. 2017; 49 : 1539-1545 Crossref PubMed Scopus (9) Google Scholar , 2 Osterwalder M. et al. Enhancer redundancy provides phenotypic robustness in mammalian development. Nature. 2018; 554 : 239-243 Crossref PubMed Scopus (10) Google Scholar , 3 Dickel D.E. et al. Ultraconserved enhancers are required for normal development. Cell. 2018; 172 : 491-499 Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar , 4 Gonen N. et al. Sex reversal following deletion of a single distal enhancer of Sox9. Science. 2018; 360 : 1469-1473 Crossref PubMed Scopus (1) Google Scholar , 5 Cunningham T.J. et al. Genomic knockout of two presumed forelimb Tbx5 enhancers reveals they are nonessential for limb development. Cell Rep. 2018; 23 : 3146-3151 Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar ]. In one case, knockout of one presumed testis enhancer for Sox9 had no effect on testis development, whereas knockout of another single testis enhancer reduced expression enough to result in reversal to an ovary fate [ 4 Gonen N. et al. Sex reversal following deletion of a single distal enhancer of Sox9. Science. 2018; 360 : 1469-1473 Crossref PubMed Scopus (1) Google Scholar ]. In some cases, knockout of two presumed enhancers significantly reduced the expression of a nearby gene and resulted in a physiological defect, thus clearly demonstrating a required function and revealing enhancer redundancy [ 1 Will A.J. et al. Composition and dosage of a multipartite enhancer cluster control developmental expression of Ihh (Indian hedgehog). Nat. Genet. 2017; 49 : 1539-1545 Crossref PubMed Scopus (9) Google Scholar , 2 Osterwalder M. et al. Enhancer redundancy provides phenotypic robustness in mammalian development. Nature. 2018; 554 : 239-243 Crossref PubMed Scopus (10) Google Scholar , 3 Dickel D.E. et al. Ultraconserved enhancers are required for normal development. Cell. 2018; 172 : 491-499 Abstract Full Text Full Text PDF PubMed Scopus (11) Google
%U https://www.cell.com/trends/genetics/fulltext/S0168-9525(18)30171-9