title: An evolutionarily conserved three-dimensional structure in the vertebrate Irx clusters facilitates enhancer sharing and coregulation.
abstract: Developmental gene clusters are paradigms for the study of gene regulation; however, the mechanisms that mediate phenomena such as coregulation and enhancer sharing remain largely elusive. Here we address this issue by analysing the vertebrate Irx clusters. We first present a deep enhancer screen of a 2-Mbp span covering the IrxA cluster. Using chromosome conformation capture, we show that enhancer sharing is widespread within the cluster, explaining its evolutionarily conserved organization. We also identify a three-dimensional architecture, probably formed through interactions with CCCTC-binding factor, which is present within both Irx clusters of mouse, Xenopus and zebrafish. This architecture brings the promoters of the first two genes together in the same chromatin landscape. We propose that this unique and evolutionarily conserved genomic architecture of the vertebrate Irx clusters is essential for the coregulation of the first two genes and simultaneously maintains the third gene in a partially independent regulatory landscape.
authors.affiliation: Centro Andaluz de Biología del Desarrollo, Consejo Superior de Investigaciones Científicas and Universidad Pablo de Olavide, Carretera de Utrera Km1, 41013 Sevilla, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Tena
authors.forename: M Eva
authors.initials: ME
authors.lastname: Alonso
authors.forename: Elisa
authors.initials: E
authors.lastname: de la Calle-Mustienes
authors.forename: Erik
authors.initials: E
authors.lastname: Splinter
authors.forename: Wouter
authors.initials: W
authors.lastname: de Laat
authors.forename: Miguel
authors.initials: M
authors.lastname: Manzanares
authors.forename: José Luis
authors.initials: JL
authors.lastname: Gómez-Skarmeta
mesh_terms: D000818:Animals; D000076246:CCCTC-Binding Factor; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D005810:Multigene Family; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014981:Xenopus / Q000196:embryology / Q000235:genetics*; D029867:Xenopus Proteins / Q000235:genetics; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics
chemical_list: D000076246:CCCTC-Binding Factor; C000619698:Ctcf protein, mouse; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; D029961:Zebrafish Proteins