An evolutionarily conserved three-dimensional structure in the vertebrate Irx clusters facilitates enhancer sharing and coregulation

Juan J. Tena, M. Eva Alonso, Elisa de la Calle-Mustienes, Erik Splinter, Wouter de Laat, Miguel Manzanares and José Luis Gómez-Skarmeta ()
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Juan J. Tena: Centro Andaluz de Biología del Desarrollo, Consejo Superior de Investigaciones Científicas and Universidad Pablo de Olavide, Carretera de Utrera Km1
M. Eva Alonso: CNIC, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Melchor Fernandez Almagro 3
Elisa de la Calle-Mustienes: Centro Andaluz de Biología del Desarrollo, Consejo Superior de Investigaciones Científicas and Universidad Pablo de Olavide, Carretera de Utrera Km1
Erik Splinter: Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalaan 8
Wouter de Laat: Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalaan 8
Miguel Manzanares: CNIC, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Melchor Fernandez Almagro 3
José Luis Gómez-Skarmeta: Centro Andaluz de Biología del Desarrollo, Consejo Superior de Investigaciones Científicas and Universidad Pablo de Olavide, Carretera de Utrera Km1

Nature Communications, 2011, vol. 2, issue 1, 1-9

Abstract: 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.

Date: 2011
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DOI: 10.1038/ncomms1301

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