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Cited by 478Genomics and Chromatin DynamicsDevelopmental Biology and Gene RegulationRNA Research and Splicing

The zinc-finger protein Zelda is a key activator of the early zygotic genome in Drosophila

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Liang, Hsiao-Lan, Nien, Chung-Yi, Liu, Hsiao-Yun, Metzstein, Mark M., Kirov, Nikolai, Rushlow, Christine·2008·Nature
DOI 10.1038/nature07388PMC PMC2597674
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Abstract

In all animals, the initial events of embryogenesis are controlled by maternal gene products that are deposited into the developing oocyte. At some point after fertilization, control of embryogenesis is transferred to the zygotic genome in a process called the maternal-to-zygotic transition. During this time, many maternal RNAs are degraded and transcription of zygotic RNAs ensues. There is a long-standing question as to which factors regulate these events. The recent findings that microRNAs and Smaug mediate maternal transcript degradation have shed new light on this aspect of the problem. However, the transcription factor(s) that activate the zygotic genome remain elusive. The discovery that many of the early transcribed genes in Drosophila share a cis-regulatory heptamer motif, CAGGTAG and related sequences, collectively referred to as TAGteam sites raised the possibility that a dedicated transcription factor could interact with these sites to activate transcription. Here we report that the zinc-finger protein Zelda (Zld; Zinc-finger early Drosophila activator) binds specifically to these sites and is capable of activating transcription in transient transfection assays. Mutant embryos lacking zld are defective in cellular blastoderm formation, and fail to activate many genes essential for cellularization, sex determination and pattern formation. Global expression profiling confirmed that Zld has an important role in the activation of the early zygotic genome and suggests that Zld may also regulate maternal RNA degradation during the maternal-to-zygotic transition.

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  • Zelda is required for correct spatial patterning of these genes: in Zelda mutants, expression of the Type III- target genes dpp and zen disappear, whereas the Type III+ gene sog diminishes and acquires the characteristics of a Type II pattern.

    “Moreover it appears that Zelda is required for correct spatial patterning of these genes: In Zelda mutants, expression of the Type III2 target genes dpp and zen disappear, whereas the Type IIIþ gene sog diminishes and acquires the characteristics of a Type II pattern”

    From Graded dorsal and differential gene regulation in the Drosophila embryo. (2009) · cites this paper as Liang et al. 2008

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

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  • Gene expression in dorsolateral regions of the embryo (Type III+) requires the function of both Dorsal and Zelda, while in dorsal regions (Type III-), Dorsal activity must be essentially absent but Zelda is still required.

    “Second, gene expression in dorsolateral regions of the embryos (Type IIIþ) requires the function of both Dorsal and Zelda, while in dorsal regions (Type III2), Dorsal activity must be essentially absent but Zelda is still required”

    From Graded dorsal and differential gene regulation in the Drosophila embryo. (2009) · cites this paper as Liang et al. 2008

    The indexed passage (labelled Abstract; page unavailable) says that both Dorsal and Zelda contribute to the broad lateral sog expression domain where Dorsal levels are low. It also reports that zen and dpp were not activated without Zelda. It does not establish that Dorsal activity must be essentially absent in the dorsal region or define the Type III+/III− categories. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • 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 [33]

    The paper’s Abstract reports that Zelda binds regulatory TAGteam sites and plays a key role in activating the early zygotic genome. It does not say that Zelda lowers a nucleosome barrier at enhancers; the passages retrieved for nucleosome occupancy and chromatin accessibility do not establish that mechanism. No page numbers are available in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Cites

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Research works printed but not linked: 28

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Authors
Liang, H.-L., Nien, C.-Y., Liu, H.-Y., Metzstein, M. M., Kirov, N., & Rushlow, C.
Affiliations
  • New York University (US)
  • University of Utah (US)
Corresponding author
Rushlow, Christine
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2008-10-19
Volume
456
Issue
7220
Pages
400-403
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature07388
PMC
PMC2597674
OpenAlex
W2073761355
Cited by
478
References
2
Citations by year
2026: 18 · 2025: 21 · 2024: 29 · 2023: 28 · 2022: 36 · 2021: 25 · 2020: 30 · 2019: 33 · 2018: 35 · 2017: 35 · 2016: 32 · 2015: 27 · 2014: 33 · 2013: 24 · 2012: 24
FWCI
6.59
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of General Medical Sciences (R01GM063024, GM-63024)
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 › RNA Research and Splicing
Keywords
Zelda, zinc finger proteins, zygotic genome activation, maternal-to-zygotic transition, transcriptional activation, cellularization, sex determination, dorsoventral patterning, Drosophila embryogenesis, transcription factor binding specificity, global gene expression profiling, microRNA
MeSH terms
Animals, Blastoderm, Drosophila melanogaster, Female, Male, Nuclear Proteins, Transcription Factors, Zygote, Transcriptional Activation, Zinc Fingers, Gene Deletion, Gene Expression Regulation, Developmental, Body Patterning, Sex Determination Processes, Gene Expression Profiling, RNA Stability, RNA, Messenger, Stored, Drosophila Proteins, Genome, Insect

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