title: Transcriptional and epigenetic signatures of zygotic genome activation during early Drosophila embryogenesis.
abstract: BACKGROUND
  In all Metazoa, transcription is inactive during the first mitotic cycles after fertilisation. In Drosophila melanogaster, Zygotic Genome Activation (ZGA) occurs in two waves, starting respectively at mitotic cycles 8 (approximately 60 genes) and 14 (over a thousand genes). The regulatory mechanisms underlying these drastic transcriptional changes remain largely unknown.
  
  
  RESULTS
  We developed an original gene clustering method based on discretized transition profiles, and applied it to datasets from three landmark early embryonic transcriptome studies. We identified 417 genes significantly up-regulated during ZGA. De novo motif discovery returned nine motifs over-represented in their non-coding sequences (upstream, introns, UTR), three of which correspond to previously known transcription factors: Zelda, Tramtrack and Trithorax-like (Trl). The nine discovered motifs were combined 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 regulation might play an important role in zygotic genome activation. We thus systematically compared the locations of predicted CRMs with ChIP-seq profiles for various transcription factors, 38 epigenetic marks from ModENCODE, and DNAse1 accessibility profiles. This analysis highlighted a strong and specific enrichment of predicted ZGA-associated CRMs for Zelda, CBP, Trl binding sites, as well as for histone marks associated with active enhancers (H3K4me1) and for open chromatin regions.
  
  
  CONCLUSIONS
  Based on the results of our computational analyses, we suggest a temporal model explaining the onset of 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-seq datasets, the resulting model suggests novel mechanisms that underly the coordinated activation of several hundreds genes at a precise time point during embryonic development.
authors.affiliation: Technological Advances for Genomics and Clinics (TAGC), INSERM U1090, Université de la Méditerranée, Campus de Luminy, 13288 Marseille Cedex 9, France. darbo@tagc.univ-mrs.fr
authors.forename: Elodie
authors.initials: E
authors.lastname: Darbo
authors.forename: Carl
authors.initials: C
authors.lastname: Herrmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Lecuit
authors.forename: Denis
authors.initials: D
authors.lastname: Thieffry
authors.forename: Jacques
authors.initials: J
authors.lastname: van Helden
mesh_terms: D000818:Animals; D001483:Base Sequence; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D016678:Genome / Q000235:genetics*; D005810:Multigene Family / Q000235:genetics; D059372:Nucleotide Motifs / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*; D015053:Zygote / Q000378:metabolism*
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