Chromatin regulates origin activity in Drosophila follicle cells.
It is widely believed that DNA replication in multicellular animals (metazoa) begins at specific origins to which a pre-replicative complex (pre-RC) binds. Nevertheless, a consensus sequence for origins has yet to be identified in metazoa. Origin identity can change during development, suggesting that there are epigenetic influences. A notable example of developmental specificity occurs in Drosophila, where somatic follicle cells of the ovary transition from genomic replication to exclusive re-replication at origins that control amplification of the eggshell (chorion) protein genes. Here we show that chromatin acetylation is critical for this developmental transition in origin specificity. We find that histones at the active origins are hyperacetylated, coincident with binding of the origin recognition complex (ORC). Mutation of the histone deacetylase (HDAC) Rpd3 induced genome-wide hyperacetylation, genomic replication and a redistribution of the origin-binding protein ORC2 in amplification-stage cells, independent of effects on transcription. Tethering Rpd3 or Polycomb proteins to the origin decreased its activity, whereas tethering the Chameau acetyltransferase increased origin activity. These results suggest that nucleosome acetylation and other epigenetic changes are important modulators of origin activity in metazoa.
Aggarwal
Bhagwan D
BD
Department of Genetics, University of Pennsylvania School of Medicine, 415 Curie Blvd, Philadelphia, Pennsylvania 19104, USA.
Calvi
Brian R
BR
D000107:Acetylation / Q000187:drug effects; D000546:Amanitins / Q000494:pharmacology; D000818:Animals; D002087:Butyrates / Q000494:pharmacology; D002823:Chorion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002843:Chromatin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics*; D005260:Female; D056284:Histone Deacetylase 1; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006358:Hot Temperature; D006877:Hydroxamic Acids / Q000494:pharmacology; D017404:In Situ Hybridization, Fluorescence; D009154:Mutation / Q000235:genetics; D009707:Nucleosomes / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D051738:Origin Recognition Complex; D006080:Ovarian Follicle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D018741:Replication Origin / Q000187:drug effects / Q000502:physiology*; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D000546:Amanitins; D002087:Butyrates; D002843:Chromatin; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D009707:Nucleosomes; C497216:Orc2 protein, Drosophila; D051738:Origin Recognition Complex; D012097:Repressor Proteins; D014157:Transcription Factors; C012589:trichostatin A; C512966:HDAC1 protein, Drosophila; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases