title: The Xenopus homologue of Down syndrome critical region protein 6 drives dorsoanterior gene expression and embryonic axis formation by antagonising polycomb group proteins.
abstract: Mesoderm and embryonic axis formation in vertebrates is mediated by maternal and zygotic factors that activate the expression of target genes. Transcriptional derepression plays an important role in the regulation of expression in different contexts; however, its involvement and possible mechanism in mesoderm and embryonic axis formation are largely unknown. Here we demonstrate that XDSCR6, a Xenopus homologue of human Down syndrome critical region protein 6 (DSCR6, or RIPPLY3), regulates mesoderm and embryonic axis formation through derepression of polycomb group (PcG) proteins. Xdscr6 maternal mRNA is enriched in the endoderm of the early gastrula and potently triggers the formation of dorsal mesoderm and neural tissues in ectoderm explants; it also dorsalises ventral mesoderm during gastrulation and induces a secondary embryonic axis. A WRPW motif, which is present in all DSCR6 homologues, is necessary and sufficient for the dorsal mesoderm- and axis-inducing activity. Knockdown of Xdscr6 inhibits dorsal mesoderm gene expression and results in head deficiency. We further show that XDSCR6 physically interacts with PcG proteins through the WRPW motif, preventing the formation of PcG bodies and antagonising their repressor activity in embryonic axis formation. By chromatin immunoprecipitation, we demonstrate that XDSCR6 releases PcG proteins from chromatin and allows dorsal mesoderm gene transcription. Our studies suggest that XDSCR6 might function to sequester PcG proteins and identify a novel derepression mechanism implicated in embryonic induction and axis formation.
authors.affiliation: Laboratory of Developmental Biology, CNRS UMR 7622, University Pierre et Marie Curie, 9 quai Saint-Bernard, 75005 Paris, France.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Li
authors.forename: Raphaëlle
authors.initials: R
authors.lastname: Grifone
authors.forename: Audrey
authors.initials: A
authors.lastname: Saquet
authors.forename: Clémence
authors.initials: C
authors.lastname: Carron
authors.forename: De-Li
authors.initials: DL
authors.lastname: Shi
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D002843:Chromatin / Q000378:metabolism; D004314:Down Syndrome / Q000235:genetics; D004475:Ectoderm / Q000196:embryology / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D004627:Embryonic Induction; D005775:Gastrula / Q000166:cytology; D054262:Gastrulation; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism*; D063146:Polycomb-Group Proteins / Q000096:biosynthesis / Q000378:metabolism*; D012333:RNA, Messenger; D019170:Somites / Q000196:embryology; D014157:Transcription Factors; D014158:Transcription, Genetic; D014981:Xenopus / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D063146:Polycomb-Group Proteins; C586306:RIPPLY3 protein, Xenopus; D012333:RNA, Messenger; D014157:Transcription Factors; D029867:Xenopus Proteins
keywords: Down syndrome; Embryonic axis formation; Mesoderm induction; Polycomb group proteins; Transcriptional derepression; Xenopus