title: Initiation of diverse epigenetic states during nuclear programming of the Drosophila body plan.
abstract: Epigenetic patterns of histone modifications contribute to the maintenance of tissue-specific gene expression. Here, we show that such modifications also accompany the specification of cell identities by the NF-κB transcription factor Dorsal in the precellular Drosophila embryo. We provide evidence that the maternal pioneer factor, Zelda, is responsible for establishing poised RNA polymerase at Dorsal target genes before Dorsal-mediated zygotic activation. At the onset of cell specification, Dorsal recruits the CBP/p300 coactivator to the regulatory regions of defined target genes in the presumptive neuroectoderm, resulting in their histone acetylation and transcriptional activation. These genes are inactive in the mesoderm due to transcriptional quenching by the Snail repressor, which precludes recruitment of CBP and prevents histone acetylation. By contrast, inactivation of the same enhancers in the dorsal ectoderm is associated with Polycomb-repressed H3K27me3 chromatin. Thus, the Dorsal morphogen gradient produces three distinct histone signatures including two modes of transcriptional repression, active repression (hypoacetylation), and inactivity (H3K27me3). Whereas histone hypoacetylation is associated with a poised polymerase, H3K27me3 displaces polymerase from chromatin. Our results link different modes of RNA polymerase regulation to separate epigenetic patterns and demonstrate that developmental determinants orchestrate differential chromatin states, providing new insights into the link between epigenetics and developmental patterning.
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 10691 Stockholm, Sweden.
authors.forename: Ann
authors.initials: A
authors.lastname: Boija
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 10691 Stockholm, Sweden mattias.mannervik@su.se.
authors.forename: Mattias
authors.identifier: 0000-0003-4999-9655
authors.initials: M
authors.lastname: Mannervik
mesh_terms: D000107:Acetylation; D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000378:metabolism; D054258:Neural Plate / Q000196:embryology / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D006657:Histones; D009687:Nuclear Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; C062236:dl protein, Drosophila; D050880:p300-CBP Transcription Factors
keywords: Dorsal morphogen; Drosophila embryo; Zelda; cell specification; epigenetics