Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo
Open accessAbstract
The transition from a specified germ cell to a population of pluripotent cells occurs rapidly following fertilization. During this developmental transition, the zygotic genome is largely transcriptionally quiescent and undergoes significant chromatin remodeling. In Drosophila, the DNA-binding protein Zelda (also known as Vielfaltig) is required for this transition and for transcriptional activation of the zygotic genome. Open chromatin is associated with Zelda-bound loci, as well as more generally with regions of active transcription. Nonetheless, the extent to which Zelda influences chromatin accessibility across the genome is largely unknown. Here we used formaldehyde-assisted isolation of regulatory elements to determine the role of Zelda in regulating regions of open chromatin in the early embryo. We demonstrate that Zelda is essential for hundreds of regions of open chromatin. This Zelda-mediated chromatin accessibility facilitates transcription-factor recruitment and early gene expression. Thus, Zelda possesses some key characteristics of a pioneer factor. Unexpectedly, chromatin at a large subset of Zelda-bound regions remains open even in the absence of Zelda. The GAGA factor-binding motif and embryonic GAGA factor binding are specifically enriched in these regions. We propose that both Zelda and GAGA factor function to specify sites of open chromatin and together facilitate the remodeling of the early embryonic genome.
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In Drosophila, Zelda is critical for lowering the nucleosome barrier at enhancers for genes driving zygotic gene activation.
“In Drosophila, the Zinc Finger Early Drosophila Activator (Zelda) is critical for lowering the nucleosome barrier at enhancers for genes driving zygotic gene activation [33–35].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [35]
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Pioneer transcription factors: establishing competence for gene expression
Zaret, K. S., & Carroll, J. S. (2011) · Genes & Development · doi:10.1101/gad.176826.111 · Cited by 1,589 · see citing works
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Newport, J., & Kirschner, M. (1982) · Cell · doi:10.1016/0092-8674(82)90273-2 · Cited by 1,055 · see citing works
Pioneer Transcription Factors Target Partial DNA Motifs on Nucleosomes to Initiate Reprogramming
Soufi, A., Garcia, M. F., Jaroszewicz, A., Osman, N., Pellegrini, M., & Zaret, K. S. (2015) · Cell · doi:10.1016/j.cell.2015.03.017 · Cited by 780 · cited 1× · see citing works
“Furthermore, Pou5f3 and Sox2 are known to be pioneer factors instrumental in reprogramming differentiated cells to a pluripotent state (Soufi et al. 2012, 2015).”
BackgroundHarrison, M. M., Li, X.-Y., Kaplan, T., Botchan, M. R., & Eisen, M. B. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002266 · Cited by 338 · see citing works
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Chromatin accessibility and the regulatory epigenome
Klemm, S. L., Shipony, Z., & Greenleaf, W. J. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-018-0089-8 · Cited by 1,793 · see citing works
Transcriptional enhancers and their communication with gene promoters
Ray-Jones, H., & Spivakov, M. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03903-w · Cited by 81 · see citing works
- Authors
- Schulz, K. N., Bondra, E. R., Moshe, A., Villalta, J. E., Lieb, J. D., Kaplan, T., McKay, D. J., & Harrison, M. M.
- Affiliations
- University of Wisconsin–Madison (US)
- Hebrew University of Jerusalem (IL)
- Howard Hughes Medical Institute (US)
- University of Chicago (US)
- University of North Carolina at Chapel Hill (US)
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2015-09-02
- Volume
- 25
- Issue
- 11
- Pages
- 1715-1726
- ISSN
- 1088-9051 (ISSN-L)
- 1549-5469
- PMC
- PMC4617967
- OpenAlex
- W4300102919
- Cited by
- 177
- References
- 4
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 19 · 2023: 12 · 2022: 21 · 2021: 19 · 2020: 19 · 2019: 23 · 2018: 21 · 2017: 19 · 2016: 4
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health (T32 GM07215)
- Basil O'Connor Starter Scholar Research award (5-FY14-29)
- National Institute of General Medical Sciences (1R01GM111694)
- 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 › Epigenetics and DNA Methylation
- Keywords
- Zelda, chromatin accessibility, open chromatin, transcription factor binding, pioneer factors, GAGA factor, zygotic genome activation, chromatin remodeling, gene expression
- MeSH terms
- Animals, Chromatin, DNA-Binding Proteins, Drosophila melanogaster, Female, Male, Nuclear Proteins, Promoter Regions, Genetic, Regulatory Sequences, Nucleic Acid, Transcription Factors, Transcriptional Activation, Sequence Analysis, DNA, Gene Expression Regulation, Developmental, Drosophila Proteins, Genetic Loci, Genetic Association Studies
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