Multi-enhancer transcriptional hubs confer phenotypic robustness.

作者: Albert Tsai , Mariana RP Alves , Justin Crocker

DOI: 10.7554/ELIFE.45325

关键词: Drosophila melanogasterTranscription factorCell biologyTranscriptional regulationTranscription (biology)Locus (genetics)Gene expressionBiologyEnhancerUltrabithorax

摘要: We previously showed in Drosophila melanogaster embryos that low-affinity Ultrabithorax (Ubx)-responsive shavenbaby (svb) enhancers drive expression using localized transcriptional environments and active svb on different chromosomes tended to colocalize (Tsai et al., 2017). Here, we test the hypothesis these multi-enhancer 'hubs' improve phenotypic resilience stress by buffering against decreases transcription factor concentrations output. Deleting a redundant enhancer from locus led reduced trichome numbers raised at elevated temperatures. Using high-resolution fluorescence microscopy, observed lower Ubx concentration output this deletion allele. Transcription sites of full cis-regulatory region inserted into chromosome colocalized with locus, increasing concentration, svb, partially rescuing phenotype. Thus, multiple could reinforce local hub buffer environmental stresses genetic perturbations, providing mechanism for phenotypical robustness.

参考文章(57)
M. Peifer, W. Bender, The anterobithorax and bithorax mutations of the bithorax complex. The EMBO Journal. ,vol. 5, pp. 2293- 2303 ,(1986) , 10.1002/J.1460-2075.1986.TB04497.X
Davide Normanno, Lydia Boudarène, Claire Dugast-Darzacq, Jiji Chen, Christian Richter, Florence Proux, Olivier Bénichou, Raphaël Voituriez, Xavier Darzacq, Maxime Dahan, None, Probing the target search of DNA-binding proteins in mammalian cells using TetR as model searcher Nature Communications. ,vol. 6, pp. 7357- 7357 ,(2015) , 10.1038/NCOMMS8357
FranÇois Payre, Alain Vincent, Sebastien Carreno, ovo/svb integrates Wingless and DER pathways to control epidermis differentiation Nature. ,vol. 400, pp. 271- 275 ,(1999) , 10.1038/22330
Nicolás Frankel, Gregory K. Davis, Diego Vargas, Shu Wang, François Payre, David L. Stern, Phenotypic robustness conferred by apparently redundant transcriptional enhancers Nature. ,vol. 466, pp. 490- 493 ,(2010) , 10.1038/NATURE09158
Koen J T Venken, Joseph W Carlson, Karen L Schulze, Hongling Pan, Yuchun He, Rebecca Spokony, Kenneth H Wan, Maxim Koriabine, Pieter J de Jong, Kevin P White, Hugo J Bellen, Roger A Hoskins, Versatile P[acman] BAC libraries for transgenesis studies in Drosophila melanogaster Nature Methods. ,vol. 6, pp. 431- 434 ,(2009) , 10.1038/NMETH.1331
Isabelle Delon, Hélène Chanut-Delalande, François Payre, The Ovo/Shavenbaby transcription factor specifies actin remodelling during epidermal differentiation in Drosophila Mechanisms of Development. ,vol. 120, pp. 747- 758 ,(2003) , 10.1016/S0925-4773(03)00081-9
Justin Crocker, Namiko Abe, Lucrezia Rinaldi, Alistair P. McGregor, Nicolás Frankel, Shu Wang, Ahmad Alsawadi, Philippe Valenti, Serge Plaza, François Payre, Richard S. Mann, David L. Stern, Low affinity binding site clusters confer hox specificity and regulatory robustness. Cell. ,vol. 160, pp. 191- 203 ,(2015) , 10.1016/J.CELL.2014.11.041
J.-W. Hong, D. A. Hendrix, M. S. Levine, Shadow enhancers as a source of evolutionary novelty. Science. ,vol. 321, pp. 1314- 1314 ,(2008) , 10.1126/SCIENCE.1160631
Yad Ghavi-Helm, Felix A. Klein, Tibor Pakozdi, Lucia Ciglar, Daan Noordermeer, Wolfgang Huber, Eileen E. M. Furlong, Enhancer loops appear stable during development and are associated with paused polymerase Nature. ,vol. 512, pp. 96- 100 ,(2014) , 10.1038/NATURE13417
William McGinnis, Robb Krumlauf, Homeobox genes and axial patterning Cell. ,vol. 68, pp. 283- 302 ,(1992) , 10.1016/0092-8674(92)90471-N