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


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.

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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.

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Gene Expression Omnibus

Data deposits

The microarray data have been deposited in NCBI’s Gene Expression Omnibus (GEO; and are accessible through GEO series accession number GSE11231.


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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).

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Correspondence to Christine Rushlow.

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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).

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