Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

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

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 ensues1. There is a long-standing question as to which factors regulate these events. The recent findings that microRNAs2,3 and Smaug4 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 sequences5,6, collectively referred to as TAGteam sites5 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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: TAGteam sites bind Zld and mediate transcriptional activation.
Figure 2: Maternal zld transcripts are lost as zygotic zld is activated in cycle 14.
Figure 3: Maternal zld is required for cellularization.
Figure 4: Zld plays a role in zygotic gene activation and maternal RNA degradation during the MZT.

Similar content being viewed by others

Accession codes

Primary accessions

Gene Expression Omnibus

Data deposits

The microarray data have been deposited in NCBI’s Gene Expression Omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo/) and are accessible through GEO series accession number GSE11231.

References

  1. Newport, J. & Kirschner, M. A major developmental transition in early Xenopus embryos: II. Control of the onset of transcription. Cell 30, 687–696 (1982)

    Article  CAS  PubMed  Google Scholar 

  2. Giraldez, A. J. et al. Zebrafish miR-430 promotes deadenylation and clearance of maternal mRNAs. Science 312, 75–79 (2006)

    Article  ADS  CAS  PubMed  Google Scholar 

  3. Bushati, N., Stark, A., Brennecke, J. & Cohen, S. Temporal reciprocity of miRNAs and their targets during the maternal-to-zygotic transition in Drosophila . Curr. Biol. 18, 501–506 (2008)

    Article  CAS  PubMed  Google Scholar 

  4. Tadros, W. et al. SMAUG is a major regulator of maternal mRNA destabilization in Drosophila and its translation is activated by the PAN GU kinase. Dev. Cell 12, 143–155 (2007)

    Article  CAS  PubMed  Google Scholar 

  5. ten Bosch, J. R., Benavides, J. A. & Cline, T. W. The TAGteam DNA motif controls the timing of Drosophila pre-blastoderm transcription. Development 133, 1967–1977 (2006)

    Article  CAS  PubMed  Google Scholar 

  6. De Renzis, S. D., Elemento, O., Tavazoie, S. & Wieschaus, E. F. Unmasking activation of the zygotic genome using chromosomal deletions in the Drosophila embryo. PLoS Biol. 5, 1036–1051 (2007)

    Article  CAS  Google Scholar 

  7. Li, X. et al. Transcription factors bind thousands of active and inactive regions in the Drosophila blastoderm. PLoS Biol. 6, 365–388 (2008)

    CAS  Google Scholar 

  8. Jiang, J., Rushlow, C. A., Zhou, Q., Small, S. & Levine, M. Individual Dorsal morphogen binding sites mediate activation and repression in the Drosophila embryo. EMBO J. 11, 3147–3154 (1992)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kirov, N., Zhelnin, L., Shah, J. & Rushlow, C. Conversion of a silencer into an enhancer: evidence for a co-repressor in dorsal-mediated repression in Drosophila . EMBO J. 12, 3193–3199 (1993)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Staudt, N., Fellert, S., Chung, H., Jäckle, H. & Vorbrüggen, G. Mutations of the Drosophila zinc finger-encoding gene vielfältig impair mitotic cell divisions and cause improper chromosome segregation. Mol. Biol. Cell 17, 2356–2365 (2006)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bourbon, H. M. et al. A P-insertion screen identifying novel X-linked essential genes in Drosophila . Mech. Dev. 110, 71–83 (2002)

    Article  CAS  PubMed  Google Scholar 

  12. Simpson, L. & Wieschaus, E. F. Zygotic activity of the nullo locus is required to stabilize the actin-myosin network during cellularizatiron in Drosophila . Development 110, 851–863 (1990)

    CAS  PubMed  Google Scholar 

  13. Schweisguth, F., Lepesant, J. A. & Vincent, A. The serendipity alpha gene encodes a membrane-associated protein required for the cellularization of the Drosophila embryo. Genes Dev. 4, 922–931 (1990)

    Article  CAS  PubMed  Google Scholar 

  14. Lecuit, T., Samanta, R. & Wieschaus, E. slam encodes a developmental regulator of polarized membrane growth during cleavage of the Drosophila embryo. Dev. Cell 2, 425–436 (2002)

    Article  CAS  PubMed  Google Scholar 

  15. Stein, J. A., Broihier, H. T., Moor, L. A. & Lehmann, R. Slow as molasses is required for polarized membrane growth and germ cell migration in Drosophila . Development 129, 3925–3934 (2002)

    CAS  PubMed  Google Scholar 

  16. Grosshans, J., Müller, H. & Wieschaus, E. Control of cleavage cycles in Drosophila embryos by frühstart . Dev. Cell 5, 285–294 (2003)

    Article  CAS  PubMed  Google Scholar 

  17. Robinson, D. N. & Cooley, L. Examination of the function of two kelch proteins generated by stop codon suppression. Development 124, 1405–1417 (1997)

    CAS  PubMed  Google Scholar 

  18. Stathopoulos, A. & Levine, M. Genomic regulatory networks and animal development. Dev. Cell 9, 449–462 (2005)

    Article  CAS  PubMed  Google Scholar 

  19. Markstein, M., Markstein, P., Markstein, V. & Levine, M. S. Genome-wide analysis of clustered Dorsal binding sites identifies putative target genes in the Drosophila embryo. Proc. Natl Acad. Sci. USA 99, 763–768 (2002)

    Article  ADS  CAS  PubMed  Google Scholar 

  20. Gross, S. P., Guo, Y., Martinez, J. E. & Welte, M. A. A determinant for directionality of organelle transport in Drosophila embryos. Curr. Biol. 13, 1660–1668 (2003)

    Article  CAS  PubMed  Google Scholar 

  21. Pilot, F., Philippe, J. M., Lemmers, C., Chauvin, J. P. & Lecuit, T. Developmental control of nuclear morphogenesis and anchoring by charleston, identified in a functional genomic screen of Drosophila cellularization. Development 133, 711–723 (2006)

    Article  CAS  PubMed  Google Scholar 

  22. Biemar, F. et al. Spatial regulation of microRNA gene expression in the Drosophila embryo. Proc. Natl Acad. Sci. USA 102, 15907–15911 (2005)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gunsalus, K. C. et al. Predictive models of molecular machines involved in Caenorhabditis elegans early embryogenesis. Nature 436, 861–865 (2005)

    Article  ADS  CAS  PubMed  Google Scholar 

  24. Ryder, E. et al. The DrosDel collection: a set of P-element insertions for generating custom chromosomal aberrations in Drosophila melanogaster . Genetics 167, 797–813 (2004)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Chou, T. B., Noll, E. & Perrimon, N. Autosomal P[ovoD1] dominant female-sterile insertions in Drosophila and their use in generating germ-line chimeras. Development 119, 1359–1369 (1993)

    CAS  PubMed  Google Scholar 

  26. Chou, T. B. & Perrimon, N. The autosomal FLP-DFS technique for generating germline mosaics in Drosophila melanogaster . Genetics 144, 1673–1679 (1996)

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Yu, Y. et al. The nuclear hormone receptor Ftz-F1 is a cofactor for the Drosophila homeodomain protein. Nature 385, 552–555 (1997)

    Article  ADS  CAS  PubMed  Google Scholar 

  28. Kirkpatrick, H., Johnson, K. & Laughon, A. Repression of dpp targets by binding of brinker to mad sites. J. Biol. Chem. 276, 18216–18222 (2001)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the following people for gifts of RNA probes, plasmids, antibodies and fly stocks: J. Erickson, R. Lehmann, R. Cinalli, R. Martinho, C. Navarro, J. Treisman and L. Pick. We thank J. Rhee and A. Chung for help with isolating and characterizing zld null mutants, and S. Fu for help locating TAGteam sites in Zelda target genes. We are grateful to M. Siegel and K. Birnbaum for help with the microarray analysis, and C. Desplan, P. Struffi, S. Small and R. Lehmann for critical reading of the manuscript. This work was supported by a grant from the National Institutes of Health (GM63024).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christine Rushlow.

Supplementary information

Supplementary Information

This file contains Supplementary Methods, Supplementary Figures S1 and S2 with Legends, Supplementary Tables S1 and S2 and Supplementary References. (PDF 1462 kb)

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liang, HL., Nien, CY., Liu, HY. et al. The zinc-finger protein Zelda is a key activator of the early zygotic genome in Drosophila. Nature 456, 400–403 (2008). https://doi.org/10.1038/nature07388

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature07388

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing