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Shadow Enhancers Mediate Dynamic Shifts of Gap Gene Expression in the Drosophila Embryo

2016; Elsevier BV; Volume: 26; Issue: 9 Linguagem: Inglês

10.1016/j.cub.2016.02.054

1879-0445

Ezzat El‐Sherif, Michael Levine,

RNA Research and Splicing

Drosophila patterning genes often contain pairs of primary and shadow enhancers that possess overlapping activities [1Hong J.W. Hendrix D.A. Levine M.S. Shadow enhancers as a source of evolutionary novelty.Science. 2008; 321: 1314Crossref PubMed Scopus (321) Google Scholar, 2Zeitlinger J. Zinzen R.P. Stark A. Kellis M. Zhang H. Young R.A. Levine M. Whole-genome ChIP-chip analysis of Dorsal, Twist, and Snail suggests integration of diverse patterning processes in the Drosophila embryo.Genes Dev. 2007; 21: 385-390Crossref PubMed Scopus (238) Google Scholar, 3Cannavò E. Khoueiry P. Garfield D.A. Geeleher P. Zichner T. Gustafson E.H. Ciglar L. Korbel J.O. Furlong E.E. Shadow enhancers are pervasive features of developmental regulatory networks.Curr. Biol. 2016; 26: 38-51Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar, 4Frankel N. Davis G.K. Vargas D. Wang S. Payre F. Stern D.L. Phenotypic robustness conferred by apparently redundant transcriptional enhancers.Nature. 2010; 466: 490-493Crossref PubMed Scopus (344) Google Scholar, 5Perry M.W. Boettiger A.N. Bothma J.P. Levine M. Shadow enhancers foster robustness of Drosophila gastrulation.Curr. Biol. 2010; 20: 1562-1567Abstract Full Text Full Text PDF PubMed Scopus (263) Google Scholar]. It has been suggested that this regulatory "redundancy" helps ensure reliable activation of gene expression under stressful conditions such as increases in temperature [4Frankel N. Davis G.K. Vargas D. Wang S. Payre F. Stern D.L. Phenotypic robustness conferred by apparently redundant transcriptional enhancers.Nature. 2010; 466: 490-493Crossref PubMed Scopus (344) Google Scholar, 5Perry M.W. Boettiger A.N. Bothma J.P. Levine M. Shadow enhancers foster robustness of Drosophila gastrulation.Curr. Biol. 2010; 20: 1562-1567Abstract Full Text Full Text PDF PubMed Scopus (263) Google Scholar]. There is also evidence that shadow enhancers help produce sharp on/off boundaries of gene expression in response to small changes in the levels of regulatory factors, such as the maternal Bicoid gradient [6Perry M.W. Boettiger A.N. Levine M. Multiple enhancers ensure precision of gap gene-expression patterns in the Drosophila embryo.Proc. Natl. Acad. Sci. USA. 2011; 108: 13570-13575Crossref PubMed Scopus (159) Google Scholar, 7Bothma J.P. Garcia H.G. Ng S. Perry M.W. Gregor T. Levine M. Enhancer additivity and non-additivity are determined by enhancer strength in the Drosophila embryo.Elife. 2015; 4: e07956Crossref Google Scholar]. Here, we use live-imaging methods to visualize the temporal dynamics of the gap genes Kruppel and knirps, which are essential for the patterning of the thorax and abdomen, respectively [8Hoch M. Schröder C. Seifert E. Jäckle H. cis-acting control elements for Krüppel expression in the Drosophila embryo.EMBO J. 1990; 9: 2587-2595Crossref PubMed Scopus (88) Google Scholar, 9Pankratz M.J. Busch M. Hoch M. Seifert E. Jäckle H. Spatial control of the gap gene knirps in the Drosophila embryo by posterior morphogen system.Science. 1992; 255: 986-989Crossref PubMed Scopus (55) Google Scholar]. Previous analyses of fixed embryos suggested anterior shifts of the Kruppel and knirps expression patterns [10Jaeger J. Surkova S. Blagov M. Janssens H. Kosman D. Kozlov K.N. Manu Myasnikova E. Vanario-Alonso C.E. Samsonova M. et al.Dynamic control of positional information in the early Drosophila embryo.Nature. 2004; 430: 368-371Crossref PubMed Scopus (445) Google Scholar]. Here, we use computational visualization methods to reveal the precise temporal dynamics of these shifts and further suggest that shadow enhancers are crucial for this process. We discuss potential mechanisms for enhancer dominance, whereby one enhancer represses the other to foster temporal dynamics.