Shadow enhancers are groups of two or more enhancers that control the same target gene and drive overlapping spatiotemporal expression patterns.[1][2][3] Shadow enhancers are found in a wide range of organisms, from insects to plants to mammals, particularly in association with developmental genes.[4][5][6][7] While seemingly redundant, the individual enhancers of a shadow enhancer group have been shown to be critical for proper gene expression in the face of both environmental and genetic perturbations. Such perturbations may exacerbate fluctuations in upstream regulators.[1][8][9]

References

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  1. ^ a b Waymack, Rachel; Fletcher, Alvaro; Enciso, German; Wunderlich, Zeba (2020-08-17). Wittkopp, Patricia J; Crocker, Justin (eds.). "Shadow enhancers can suppress input transcription factor noise through distinct regulatory logic". eLife. 9: e59351. doi:10.7554/eLife.59351. ISSN 2050-084X. PMC 7556877. PMID 32804082.   This article incorporates text available under the CC BY 4.0 license.
  2. ^ Hong, Joung-Woo; Hendrix, David A.; Levine, Michael S. (2008-09-05). "Shadow Enhancers as a Source of Evolutionary Novelty". Science. 321 (5894): 1314. Bibcode:2008Sci...321.1314H. doi:10.1126/science.1160631. ISSN 0036-8075. PMC 4257485. PMID 18772429.
  3. ^ Barolo, Scott (2012). "Shadow enhancers: Frequently asked questions about distributed cis-regulatory information and enhancer redundancy". BioEssays. 34 (2): 135–141. doi:10.1002/bies.201100121. ISSN 1521-1878. PMC 3517143. PMID 22083793.
  4. ^ Cannavò, Enrico; Khoueiry, Pierre; Garfield, David A.; Geeleher, Paul; Zichner, Thomas; Gustafson, E. Hilary; Ciglar, Lucia; Korbel, Jan O.; Furlong, Eileen E.M. (January 2016). "Shadow Enhancers Are Pervasive Features of Developmental Regulatory Networks". Current Biology. 26 (1): 38–51. Bibcode:2016CBio...26...38C. doi:10.1016/j.cub.2015.11.034. ISSN 0960-9822. PMC 4712172. PMID 26687625.
  5. ^ Osterwalder, Marco; Barozzi, Iros; Tissières, Virginie; Fukuda-Yuzawa, Yoko; Mannion, Brandon J.; Afzal, Sarah Y.; Lee, Elizabeth A.; Zhu, Yiwen; Plajzer-Frick, Ingrid; Pickle, Catherine S.; Kato, Momoe (February 2018). "Enhancer redundancy provides phenotypic robustness in mammalian development". Nature. 554 (7691): 239–243. Bibcode:2018Natur.554..239O. doi:10.1038/nature25461. ISSN 1476-4687. PMC 5808607. PMID 29420474.
  6. ^ Garnett, Aaron T.; Square, Tyler A.; Medeiros, Daniel M. (2012-11-15). "BMP, Wnt and FGF signals are integrated through evolutionarily conserved enhancers to achieve robust expression of Pax3 and Zic genes at the zebrafish neural plate border". Development. 139 (22): 4220–4231. doi:10.1242/dev.081497. ISSN 0950-1991. PMC 4074300. PMID 23034628.
  7. ^ Bomblies, Kirsten; Dagenais, Nicole; Weigel, Detlef (1999-12-01). "Redundant Enhancers Mediate Transcriptional Repression of AGAMOUS by APETALA2". Developmental Biology. 216 (1): 260–264. doi:10.1006/dbio.1999.9504. ISSN 0012-1606. PMID 10588876.
  8. ^ Cheung, David; Ma, Jun (October 2015). "Probing the impact of temperature on molecular events in a developmental system". Scientific Reports. 5 (1): 13124. Bibcode:2015NatSR...513124C. doi:10.1038/srep13124. ISSN 2045-2322. PMC 4541335. PMID 26286011.
  9. ^ Chen, Jun; Nolte, Viola; Schlötterer, Christian (2015-02-26). Gibson, Greg (ed.). "Temperature Stress Mediates Decanalization and Dominance of Gene Expression in Drosophila melanogaster". PLOS Genetics. 11 (2): e1004883. doi:10.1371/journal.pgen.1004883. ISSN 1553-7404. PMC 4342254. PMID 25719753.