Transcriptional and epigenetic signatures of zygotic genome activation during early drosophila embryogenesis.
Résumé
Background; In all Metazoa, transcription is inactive during the first mitotic cycles after fertilisation. In Drosophilamelanogaster, Zygotic Genome Activation (ZGA) occurs in two waves, starting respectively at mi-totic cycles 8 (approximately 60 genes) and 14 (over a thousand genes). The regulatory mechanismsunderlying these drastic transcriptional changes remain largely unknown.Results; We developed an original gene clustering method based on discretized transition profiles, and appliedit to datasets from three landmark early embryonic transcriptome studies. We identified 417 genes sig-nificantly up-regulated during ZGA. De novo motif discovery returned nine motifs over-represented intheir non-coding sequences (upstream, introns, UTR), three of which correspond to previously knowntranscription factors: Zelda, Tramtrack and Trithorax-like (Trl). The nine discovered motifs werecombined to scan ZGA-associated regions and predict about 1300 putative cis-regulatory modules.The fact that Trl is known to act as chromatin remodelling factor suggests that epigenetic regulationmight play an important role in zygotic genome activation. We thus systematically compared thelocations of predicted CRMs with ChIP-seq profiles for various transcription factors, 38 epigeneticmarks from ModENCODE, and DNAse1 accessibility profiles. This analysis highlighted a strong andspecific enrichment of predicted ZGA-associated CRMs for Zelda, CBP, Trl binding sites, as well asfor histone marks associated with active enhancers (H3K4me1) and for open chromatin regions.Conclusion;Based on the results of our computational analyses, we suggest a temporal model explaining the onsetof zygotic genome activation by the combined action of transcription factors and epigenetic signals.Although this study is mainly based on the analysis of publicly available transcriptome and ChiP-seqdatasets, the resulting model suggests novel mechanisms that underly the coordinated activation ofseveral hundreds genes at a precise time point during embryonic development.
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