Cited by 88Genomics and Chromatin DynamicsDevelopmental Biology and Gene RegulationGene Regulatory Network Analysis

The Drosophila Pioneer Factor Zelda Modulates the Nuclear Microenvironment of a Dorsal Target Enhancer to Potentiate Transcriptional Output

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Yamada, Shigehiro, Whitney, Peter H., Huang, Shao-Kuei, Eck, Elizabeth C., Garcia, Hernan G., Rushlow, Christine A.·2019·Current Biology

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Abstract

Connecting the developmental patterning of tissues to the mechanistic control of RNA polymerase II remains a long-term goal of developmental biology. Many key elements have been identified in the establishment of spatial-temporal control of transcription in the early Drosophila embryo, a model system for transcriptional regulation. The dorsal-ventral axis of the Drosophila embryo is determined by the graded distribution of Dorsal (Dl), a homolog of the nuclear factor κB (NF-κB) family of transcriptional activators found in humans [1, 2]. A second maternally deposited factor, Zelda (Zld), is uniformly distributed in the embryo and is thought to act as a pioneer factor, increasing enhancer accessibility for transcription factors, such as Dl [3-9]. Here, we utilized the MS2 live imaging system to evaluate the expression of the Dl target gene short gastrulation (sog) to better understand how a pioneer factor affects the kinetic parameters of transcription. Our experiments indicate that Zld modifies probability of activation, the timing of this activation, and the rate at which transcription occurs. Our results further show that this effective rate increase is due to an increased accumulation of Dl at the site of transcription, suggesting that transcription factor "hubs" induced by Zld [10] functionally regulate transcription.

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Crossref · 10.1016/j.cub.2019.03.019

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  • Zelda promotes the formation of local transcription factor hubs involving transcription factors required for developmental patterning, such as Bicoid and Dorsal.

    “For instance, Zelda promotes the formation of local TF hubs involving important transcription factors required for developmental patterning, such as Bicoid and Dorsal [51–54].”

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  1. [1]Steward R, McNally FJ, and Schedl P (1984). Isolation of the dorsal locus of Drosophila. Nature 311, 262– 265. 6434990
  2. [2]Stathopoulos A, and Levine M (2002). Dorsal gradient networks in the Drosophila embryo. Dev. Biol 246, 57– 67. 12027434
  3. [3]Liang H-L, Nien C-Y, Liu H-Y, Metzstein MM, Kirov N, and Rushlow C (2008). The zinc-finger protein Zelda is a key activator of the early zygotic genome in Drosophila. Nature 456, 400– 403. 18931655 PMC2597674
  4. [4]Schulz KN, Bondra ER, Moshe A, Villalta JE, Lieb JD, Kaplan T, McKay DJ, and Harrison MM (2015). Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo. Genome Res 25, 1715– 1726. 26335634 PMC4617967
  5. [5]Nien C-Y, Liang H-L, Butcher S, Sun Y, Fu S, Gocha T, Kirov N, Manak JR, and Rushlow C (2011). Temporal coordination of gene networks by Zelda in the early Drosophila embryo. PLoS Genet 7, e1002339. 22028675 PMC3197689
  6. [6]Harrison MM, and Eisen MB (2015). Transcriptional Activation of the Zygotic Genome in Drosophila. Curr. Top. Dev. Biol 113, 85– 112. 26358871
  7. [7]Foo SM, Sun Y, Lim B, Ziukaite R, O’Brien K, Nien C-Y, Kirov N, Shvartsman SY, and Rushlow CA (2014). Zelda Potentiates Morphogen Activity by Increasing Chromatin Accessibility. Curr. Biol 24, 1341– 1346. 24909324 PMC4075064
  8. [8]Sun Y, Nien C-Y, Chen K, Liu H-Y, Johnston J, Zeitlinger J, and Rushlow C (2015). Zelda overcomes the high intrinsic nucleosome barrier at enhancers during Drosophila zygotic genome activation. Genome Res 25, 1703– 1714. 26335633 PMC4617966
  9. [10]Mir M, Reimer A, Haines JE, Li XY, Stadler M, Garcia H, Eisen MB and Darzacq X, (2017). Dense Bicoid hubs accentuate binding along the morphogen gradient. Genes Dev 31, 1784– 1794. 28982761 PMC5666676
  10. [11]Kanodia JS, Liang H-L, Kim Y, Lim B, Zhan M, Lu H, Rushlow CA, and Shvartsman SY (2012). Pattern formation by graded and uniform signals in the early Drosophila embryo. Biophys. J 102, 427– 433. 22325264 PMC3274790
  11. [12]Larson DR, Zenklusen D, Wu B, Chao JA, and Singer RH (2011). Real-time observation of transcription initiation and elongation on an endogenous yeast gene. Science 332, 475– 478. 21512033 PMC3152976
  12. [13]Forrest KM, and Gavis ER (2003). Live imaging of endogenous RNA reveals a diffusion and entrapment mechanism for nanos mRNA localization in Drosophila. Curr. Biol 13, 1159– 1168. 12867026
  13. [14]Garcia HG, Tikhonov M, Lin A, and Gregor T (2013). Quantitative imaging of transcription in living Drosophila embryos links polymerase activity to patterning. Curr. Biol 23, 2140– 2145. 24139738 PMC3828032
  14. [15]Lucas T, Ferraro T, Roelens B, De Las Heras Chanes J, Walczak AM, Coppey M, and Dostatni N (2013). Live Imaging of Bicoid-Dependent Transcription in Drosophila Embryos. Curr. Biol 23, 2135– 2139. 24139736
  15. [16]Lucas T, Tran H, Romero CAP, Guillou A, Fradin C, Coppey M, Walczak AM, and Dostatni N (2018). 3 minutes to precisely measure morphogen concentration. (2018). 3 minutes to precisely measure morphogen concentration. PLoS Genet 14, e1007676 30365533 PMC6221364
  16. [17]Wu B, Miskolci V, Sato H, Tutucci E, Kenworthy CA, Donnelly SK, Yoon YJ, Cox D, Singer RH, and Hodgson L (2015). Synonymous modification results in high-fidelity gene expression of repetitive protein and nucleotide sequences. Genes Dev 29, 876– 886. 25877922 PMC4403262
  17. [19]Ozdemir A, Ma L, White KP, and Stathopoulos A (2014). Su(H)-mediated repression positions gene boundaries along the dorsal-ventral axis of Drosophila embryos. Dev. Cell 31, 100– 113. 25313963 PMC4201238
  18. [20]Saint R, and Clarkson M (2000). Pictures in cell biology. A functional marker for Drosophila chromosomes in vivo. Trends Cell Biol 10, 553. 11121748
  19. [21]Kanodia JS, Rikhy R, Kim Y, Lund VK, DeLotto R, Lippincott-Schwartz J, and Shvartsman SY (2009). Dynamics of the Dorsal morphogen gradient. Proc. Natl. Acad. Sci. U. S. A 106, 21707– 21712. 19996178 PMC2799810
  20. [22]Liberman LM, Reeves GT, and Stathopoulos A (2009). Quantitative imaging of the Dorsal nuclear gradient reveals limitations to threshold-dependent patterning in Drosophila. Proc. Natl. Acad. Sci. U. S. A 106, 22317– 22322. 20018754 PMC2799780
  21. [23]Reeves GT, Trisnadi N, Truong TV, Nahmad M, Katz S, and Stathopoulos A (2012). Dorsal-ventral gene expression in the Drosophila embryo reflects the dynamics and precision of the dorsal nuclear gradient. Dev. Cell 22, 544– 557. 22342544 PMC3469262
  22. [24]Mir M, Stadler MR, Ortiz SA, Hannon CE, Harrison MM, Darzacq X, and Eisen MB (2018). Dynamic multifactor hubs interact transiently with sites of active transcription in embryos. Elife 7 Available at: 10.7554/eLife.40497. PMC6307861 30589412 · DOI · Paper page
  23. [25]Dufourt J, Trullo A, Hunter J, Fernandez C, Lazaro J, Dejean M, Morales L, Nait-Amer S, Schulz KN, Harrison MM, (2018). Temporal control of gene expression by the pioneer factor Zelda through transient interactions in hubs. Nat. Commun 9, 5194. 30518940 PMC6281682
  24. [26]He F, Ren J, Wang W, and Ma J (2011). A Multiscale Investigation of Bicoid-Dependent Transcriptional Events in Drosophila Embryos. PLoS One 6, e19122. 21544208 PMC3081338
  25. [27]Xu H, Sepúlveda LA, Figard L, Sokac AM, and Golding I (2015). Combining protein and mRNA quantification to decipher transcriptional regulation. Nat. Methods 12, 739– 742. 26098021 PMC4521975
  26. [28]Little SC, Tikhonov M, and Gregor T (2013). Precise Developmental Gene Expression Arises from Globally Stochastic Transcriptional Activity. Cell 154, 789– 800. 23953111 PMC3778922
  27. [29]Tsai A, Muthusamy AK, Alves MR, Lavis LD, Singer RH, Stern DL, and Crocker J (2017). Nuclear microenvironments modulate transcription from low-affinity enhancers. Elife 6 Available at: 10.7554/eLife.28975. PMC5695909 29095143 · DOI
  28. [30]Li X-Y, and Eisen MB (2018). Zelda potentiates transcription factor binding to zygotic enhancers by increasing local chromatin accessibility during early Drosophila melanogaster embryogenesis Available at: 10.1101/380857. · DOI
  29. [31]Xu Z, Chen H, Ling J, Yu D, Struffi P, and Small S (2014). Impacts of the ubiquitous factor Zelda on Bicoid-dependent DNA binding and transcription in Drosophila. Genes Dev 28, 608– 621. 24637116 PMC3967049
  30. [32]Groth AC, Fish M, Nusse R, and Calos MP (2004). Construction of transgenic Drosophila by using the site-specific integrase from phage phiC31. Genetics 166, 1775– 1782. 15126397 PMC1470814
  31. [33]Bischof J, Maeda RK, Hediger M, Karch F, and Basler K (2007). An optimized transgenesis system for Drosophila using germ-line-specific phiC31 integrases. Proc. Natl. Acad. Sci. U. S. A 104, 3312– 3317. 17360644 PMC1805588
  32. [34]Hertz GZ, and Stormo GD (1999). Identifying DNA and protein patterns with statistically significant alignments of multiple sequences. Bioinformatics 15, 563– 577. 10487864

Cited by

Sorted by citations

Authors
Yamada, S., Whitney, P. H., Huang, S.-K., Eck, E. C., Garcia, H. G., & Rushlow, C. A.
Affiliations
  • New York University (US)
  • University of California, Berkeley (US)
Corresponding author
Rushlow, Christine A.
Venue
Current Biology
Publisher
Elsevier BV
Published
2019-04
Volume
29
Issue
8
Pages
1387-1393.e5
ISSN
0960-9822 (ISSN-L)
OpenAlex
W2951271895
Cited by
88
References
3
Citations by year
2026: 9 · 2025: 16 · 2024: 9 · 2023: 10 · 2022: 7 · 2021: 15 · 2020: 13 · 2019: 9
FWCI
3.61
Type
journal article
Language
en
Open access
Locations
  • Current Biology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Science Foundation (1652236)
  • National Institutes of Health (GM63024, 5T32HD007520-20)
  • Burroughs Wellcome Fund
  • Human Frontier Science Program
  • Hellman Foundation
  • Searle Scholars Program
  • Shurl and Kay Curci Foundation
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
Keywords
Zelda, pioneer factors, Dorsal, short gastrulation, enhancer accessibility, transcriptional regulation, RNA polymerase II, transcriptional kinetics, dorsal-ventral axis, Drosophila embryo
MeSH terms
Animals, Cell Nucleus, Drosophila melanogaster, Enhancer Elements, Genetic, Nuclear Proteins, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Gene Expression Regulation, Developmental, Drosophila Proteins

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