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Shadow enhancer

Shadow enhancers are groups of two or more regulatory DNA sequences that work alongside primary enhancers to control gene expression.[1][2][3][4] First identified in Drosophila, shadow enhancers have since been identified in a wide range of organisms, including insects, plants, and mammals.[2][5][6][7][8] Shadow enhancers play a critical role in stabilizing gene expression against genetic and environmental disturbances, allowing for precise spatial and temporal control of gene expression throughout development[9][1] This article will explore the discovery of shadow enhancers, how they differ from primary enhancers, and their importance in proper development.

Discovery of shadow enhancers

Shadow enhancers were first described in 2008 by Mike Levine and his research group at the University of California, Berkeley. Their research in Drosophila investigated the transcription factor Dorsal and its target genes. Through characterization of enhancers, other than the primary enhancer, they found that these enhancers appeared to produce gene expression patterns that overlap with those produced by the primary enhancer. Initially, shadow enhancers were believed to act redundantly to the function of the primary enhancer to ensure proper gene expression, despite environmental or genetic variability.[2]

Shadow enhancers vs primary enhancers

Although both primary enhancers and shadow enhancers are regulatory components of a gene, they each have distinct roles that are crucial to proper gene expression patterns. Primary enhancers drive gene expression, while shadow enhancers work together to ensure stable gene expression and minimize variability.[10][11] This ensures that even with mutation or damage to the primary enhancer, shadow enhancers can compensate for this and ensure proper gene expression patterns.[12] Although they are both types of enhancers, shadow enhancers and primary enhancers are quite distinct in terms of their locations within the genome, their regulatory strategies and their importance in changing environments.

Importance in development

Shadow enhancers play a critical role in embryogenesis, particularly in defining body patterning.[13][14] By modulating transcriptional activation strength, timing, and location, they ensure precise control of gene expression during development.[13] Their ability to fine-tune gene expression levels helps maintain stability, allowing organisms to grow and develop properly despite environmental stresses.[9][1][12] Research has shown that shadow enhancers can compensate for mutations in primary enhancers, acting as a buffer against genetic and environmental fluctuations.[4][11][12] This buffering capacity ensures consistent and precise gene expression patterns, which are crucial for proper body development and overall developmental stability.[4][1]

References

  1. ^ a b c d 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. ^ a b c 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. ^ a b c Kvon, Evgeny Z.; Waymack, Rachel; Gad, Mario; Wunderlich, Zeba (May 2021). "Enhancer redundancy in development and disease". Nature Reviews Genetics. 22 (5): 324–336. doi:10.1038/s41576-020-00311-x. ISSN 1471-0064.
  5. ^ 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.
  6. ^ 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.
  7. ^ 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.
  8. ^ 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.
  9. ^ a b Wunderlich, Zeba; Bragdon, Meghan D. J.; Vincent, Ben J.; White, Jonathan A.; Estrada, Javier; DePace, Angela H. (2015-09-22). "Krüppel Expression Levels Are Maintained through Compensatory Evolution of Shadow Enhancers". Cell Reports. 12 (11): 1740–1747. doi:10.1016/j.celrep.2015.08.021. ISSN 2211-1247. PMC 4581983.
  10. ^ Fletcher, Alvaro; Wunderlich, Zeba; Enciso, German (2023-05-19). "Shadow enhancers mediate trade-offs between transcriptional noise and fidelity". PLOS Computational Biology. 19 (5): e1011071. Bibcode:2023PLSCB..19E1071F. doi:10.1371/journal.pcbi.1011071. ISSN 1553-7358. PMC 10234526. PMID 37205714.
  11. ^ a b Dresch, Jacqueline M; Nourie, Luke L; Conrad, Regan D; Carlson, Lindsay T; Tchantouridze, Elizabeth I; Tesfaye, Biruck; Verhagen, Eleanor; Gupta, Mahima; Borges-Rivera, Diego; Drewell, Robert A (2025-01-01). "Two coacting shadow enhancers regulate twin of eyeless expression during early Drosophila development". Genetics. 229 (1): 1–43. doi:10.1093/genetics/iyae176. ISSN 1943-2631. PMC 11708921. PMID 39607769.
  12. ^ a b c Perry, Michael W.; Boettiger, Alistair N.; Bothma, Jacques P.; Levine, Michael (September 2010). "Shadow Enhancers Foster Robustness of Drosophila Gastrulation". Current Biology. 20 (17): 1562–1567. Bibcode:2010CBio...20.1562P. doi:10.1016/j.cub.2010.07.043. ISSN 0960-9822. PMC 4257487. PMID 20797865.
  13. ^ a b Whitney, Peter H.; Shrestha, Bikhyat; Xiong, Jiahan; Zhang, Tom; Rushlow, Christine A. (2022-11-01). "Shadow enhancers modulate distinct transcriptional parameters that differentially effect downstream patterning events". Development. 149 (21): dev200940. doi:10.1242/dev.200940. ISSN 0950-1991.
  14. ^ El-Sherif, Ezzat; Levine, Michael (2016-05-09). "Shadow Enhancers Mediate Dynamic Shifts of Gap Gene Expression in the Drosophila Embryo". Current Biology. 26 (9): 1164–1169. doi:10.1016/j.cub.2016.02.054. ISSN 0960-9822. PMID 27112292.
Quelle: http://en.wikipedia.org/wiki/Shadow_enhancer