CLAMP and Zelda function together to promote Drosophila zygotic genome activation

  1. Jingyue Duan  Is a corresponding author
  2. Leila Rieder
  3. Megan M Colonnetta
  4. Annie Huang
  5. Mary Mckenney
  6. Scott Watters
  7. Girish Deshpande,
  8. William Jordan
  9. Nicolas Fawzi
  10. Erica Larschan  Is a corresponding author
  1. Brown University, United States
  2. Emory University, United States
  3. Princeton University, United States

Abstract

During the essential and conserved process of zygotic genome activation (ZGA), chromatin accessibility must increase to promote transcription. Drosophila is a well-established model for defining mechanisms that drive ZGA. Zelda (ZLD) is a key pioneer transcription factor (TF) that promotes ZGA in the Drosophila embryo. However, many genomic loci that contain GA-rich motifs become accessible during ZGA independent of ZLD. Therefore, we hypothesized that other early TFs that function with ZLD have not yet been identified, especially those that are capable of binding to GA-rich motifs such as CLAMP. Here, we demonstrate that Drosophila embryonic development requires maternal CLAMP to: 1) activate zygotic transcription; 2) increase chromatin accessibility at promoters of specific genes that often encode other essential TFs; 3) enhance chromatin accessibility and facilitate ZLD occupancy at a subset of key embryonic promoters. Thus, CLAMP functions as a pioneer factor which plays a targeted yet essential role in ZGA.

Data availability

To review GEO accession GSE152613:Go to https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE152613Enter token ihevsmiqnxexrod into the box

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Jingyue Duan

    Department of Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, United States
    For correspondence
    jd774@cornell.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6416-2250
  2. Leila Rieder

    Emory University, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Megan M Colonnetta

    Department of Molecular Biology, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5685-1670
  4. Annie Huang

    Department of Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Mary Mckenney

    Department of Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Scott Watters

    Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Girish Deshpande,

    MCB, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. William Jordan

    Department of Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Nicolas Fawzi

    Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Erica Larschan

    Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, United States
    For correspondence
    erica_larschan@brown.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2484-4921

Funding

National Institute of General Medical Sciences (F32GM109663)

  • Leila Rieder

National Institute of General Medical Sciences (K99HD092625)

  • Leila Rieder

National Institute of General Medical Sciences (R00HD092625)

  • Leila Rieder

National Institute of General Medical Sciences (R35GM126994)

  • Erica Larschan

National Science Foundation (1845734)

  • Nicolas Fawzi

National Institute of General Medical Sciences (R01GM118530)

  • Nicolas Fawzi

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Yukiko M Yamashita, Whitehead Institute/MIT, United States

Version history

  1. Preprint posted: July 15, 2020 (view preprint)
  2. Received: April 30, 2021
  3. Accepted: August 2, 2021
  4. Accepted Manuscript published: August 3, 2021 (version 1)
  5. Version of Record published: August 16, 2021 (version 2)

Copyright

© 2021, Duan et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,961
    Page views
  • 324
    Downloads
  • 22
    Citations

Article citation count generated by polling the highest count across the following sources: PubMed Central, Crossref, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Jingyue Duan
  2. Leila Rieder
  3. Megan M Colonnetta
  4. Annie Huang
  5. Mary Mckenney
  6. Scott Watters
  7. Girish Deshpande,
  8. William Jordan
  9. Nicolas Fawzi
  10. Erica Larschan
(2021)
CLAMP and Zelda function together to promote Drosophila zygotic genome activation
eLife 10:e69937.
https://doi.org/10.7554/eLife.69937

Further reading

    1. Genetics and Genomics
    2. Immunology and Inflammation
    Huiyun Lyu, Guohua Yuan ... Yan Shi
    Research Article

    Thymus-originated tTregs and in vitro induced iTregs are subsets of regulatory T cells. While they share the capacity of immune suppression, their stabilities are different, with iTregs losing their phenotype upon stimulation or under inflammatory milieu. Epigenetic differences, particularly methylation state of Foxp3 CNS2 region, provide an explanation for this shift. Whether additional regulations, including cellular signaling, could directly lead phenotypical instability requires further analysis. Here, we show that upon TCR (T cell receptor) triggering, SOCE (store-operated calcium entry) and NFAT (nuclear factor of activated T cells) nuclear translocation are blunted in tTregs, yet fully operational in iTregs, similar to Tconvs. On the other hand, tTregs show minimal changes in their chromatin accessibility upon activation, in contrast to iTregs that demonstrate an activated chromatin state with highly accessible T cell activation and inflammation related genes. Assisted by several cofactors, NFAT driven by strong SOCE signaling in iTregs preferentially binds to primed-opened T helper (TH) genes, resulting in their activation normally observed only in Tconv activation, ultimately leads to instability. Conversely, suppression of SOCE in iTregs can partially rescue their phenotype. Thus, our study adds two new layers, cellular signaling and chromatin accessibility, of understanding in Treg stability, and may provide a path for better clinical applications of Treg cell therapy.

    1. Genetics and Genomics
    Emily I Green, Etienne Jaouen ... Eric Marois
    Research Article

    Lipophorin is an essential, highly expressed lipid transport protein that is secreted and circulates in insect hemolymph. We hijacked the Anopheles coluzzii Lipophorin gene to make it co-express a single-chain version of antibody 2A10, which binds sporozoites of the malaria parasite Plasmodium falciparum. The resulting transgenic mosquitoes show a markedly decreased ability to transmit Plasmodium berghei expressing the P. falciparum circumsporozoite protein to mice. To force the spread of this anti-malarial transgene in a mosquito population, we designed and tested several CRISPR/Cas9-based gene drives. One of these is installed in, and disrupts, the pro-parasitic gene Saglin and also cleaves wild-type Lipophorin, causing the anti-malarial modified Lipophorin version to replace the wild type and hitch-hike together with the Saglin drive. Although generating drive-resistant alleles and showing instability in its gRNA-encoding multiplex array, the Saglin-based gene drive reached high levels in caged mosquito populations and efficiently promoted the simultaneous spread of the antimalarial Lipophorin::Sc2A10 allele. This combination is expected to decrease parasite transmission via two different mechanisms. This work contributes to the design of novel strategies to spread antimalarial transgenes in mosquitoes, and illustrates some expected and unexpected outcomes encountered when establishing a population modification gene drive.