title: A single three-dimensional chromatin compartment in amphioxus indicates a stepwise evolution of vertebrate Hox bimodal regulation.
abstract: The HoxA and HoxD gene clusters of jawed vertebrates are organized into bipartite three-dimensional chromatin structures that separate long-range regulatory inputs coming from the anterior and posterior Hox-neighboring regions. This architecture is instrumental in allowing vertebrate Hox genes to pattern disparate parts of the body, including limbs. Almost nothing is known about how these three-dimensional topologies originated. Here we perform extensive 4C-seq profiling of the Hox cluster in embryos of amphioxus, an invertebrate chordate. We find that, in contrast to the architecture in vertebrates, the amphioxus Hox cluster is organized into a single chromatin interaction domain that includes long-range contacts mostly from the anterior side, bringing distant cis-regulatory elements into contact with Hox genes. We infer that the vertebrate Hox bipartite regulatory system is an evolutionary novelty generated by combining ancient long-range regulatory contacts from DNA in the anterior Hox neighborhood with new regulatory inputs from the posterior side.
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD), Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide, Seville, Spain.
authors.forename: Rafael D
authors.identifier: http://orcid.org/0000-0003-4120-0140
authors.initials: RD
authors.lastname: Acemel
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD), Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide, Seville, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Tena
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD), Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide, Seville, Spain.
authors.forename: Ibai
authors.initials: I
authors.lastname: Irastorza-Azcarate
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Marlétaz
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD), Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide, Seville, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Gómez-Marín
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD), Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide, Seville, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: de la Calle-Mustienes
authors.affiliation: Université Pierre et Marie Curie Université Paris 6, CNRS, UMR 7232, Biologie Integrative des Organismes Marins (BIOM), Observatoire Océanologique de Banyuls-sur-Mer, Banyuls-sur-Mer, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bertrand
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD), Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide, Seville, Spain.
authors.forename: Sergio G
authors.initials: SG
authors.lastname: Diaz
authors.affiliation: Université Pierre et Marie Curie Université Paris 6, CNRS, UMR 7232, Biologie Integrative des Organismes Marins (BIOM), Observatoire Océanologique de Banyuls-sur-Mer, Banyuls-sur-Mer, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Aldea
authors.affiliation: Commissariat à l'Energie Atomique (CEA), Institut de Génomique (IG), Genoscope, Evry, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Aury
authors.affiliation: Commissariat à l'Energie Atomique (CEA), Institut de Génomique (IG), Genoscope, Evry, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Mangenot
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK.
authors.forename: Peter W H
authors.initials: PW
authors.lastname: Holland
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD), Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide, Seville, Spain.
authors.forename: Damien P
authors.initials: DP
authors.lastname: Devos
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD), Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide, Seville, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Maeso
authors.affiliation: Université Pierre et Marie Curie Université Paris 6, CNRS, UMR 7232, Biologie Integrative des Organismes Marins (BIOM), Observatoire Océanologique de Banyuls-sur-Mer, Banyuls-sur-Mer, France.
authors.forename: Hector
authors.initials: H
authors.lastname: Escrivá
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD), Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide, Seville, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Gómez-Skarmeta
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D002843:Chromatin / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D005121:Extremities / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D064175:Lancelets / Q000235:genetics* / Q000254:growth & development; D005810:Multigene Family; D010802:Phylogeny; D014714:Vertebrates / Q000235:genetics / Q000254:growth & development
chemical_list: D002843:Chromatin; D018398:Homeodomain Proteins; C088144:HoxA protein
references.citation: Nat Protoc. 2007;2(7):1722-33
references.pmid: 17641637
references.citation: Gigascience. 2012 Dec 27;1(1):18
references.pmid: 23587118
references.citation: Elife. 2014 Apr 29;3:e02557
references.pmid: 24843030
references.citation: Nature. 2013 Oct 24;502(7472):499-506
references.pmid: 24153303
references.citation: Development. 2013 Oct;140(19):3951-63
references.pmid: 24046316
references.citation: Science. 2013 Jun 7;340(6137):1234167
references.pmid: 23744951
references.citation: Development. 2011 Nov;138(22):4819-30
references.pmid: 22028023
references.citation: J Mol Biol. 2015 Feb 13;427(3):608-25
references.pmid: 25280896
references.citation: Genome Res. 2012 Apr;22(4):642-55
references.pmid: 22234889
references.citation: Wiley Interdiscip Rev Dev Biol. 2012 Mar-Apr;1(2):167-83
references.pmid: 23801434
references.citation: Dev Dyn. 2009 Sep;238(9):2409-17
references.pmid: 19653328
references.citation: Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W435-9
references.pmid: 16845043
references.citation: Circ Res. 2014 Aug 1;115(4):432-41
references.pmid: 24963028
references.citation: Evol Dev. 2004 Nov-Dec;6(6):423-30
references.pmid: 15509224
references.citation: J Exp Zool B Mol Dev Evol. 2004 Jul 15;302(4):384-91
references.pmid: 15287102
references.citation: Nature. 2014 Aug 7;512(7512):96-100
references.pmid: 25043061
references.citation: FEBS Lett. 2015 Oct 7;589(20 Pt A):2869-76
references.pmid: 25913784
references.citation: PLoS Biol. 2014 Jan;12(1):e1001773
references.pmid: 24465181
references.citation: Methods Cell Biol. 2004;77:201-22
references.pmid: 15602913
references.citation: Science. 2011 Oct 14;334(6053):222-5
references.pmid: 21998387
references.citation: Nature. 2012 Apr 11;485(7398):376-80
references.pmid: 22495300
references.citation: Proc Natl Acad Sci U S A. 2015 Jan 20;112(3):803-8
references.pmid: 25535365
references.citation: Evodevo. 2012 Dec 03;3(1):28
references.pmid: 23198682
references.citation: Mol Cell. 2012 Nov 9;48(3):471-84
references.pmid: 23041285
references.citation: Dev Biol. 2007 Jun 15;306(2):847-59
references.pmid: 17448461
references.citation: Dev Genes Evol. 2008 Dec;218(11-12):703-13
references.pmid: 18843503
references.citation: Dev Biol. 2001 Sep 15;237(2):270-81
references.pmid: 11543613
references.citation: Biotechniques. 2003 Feb;34(2):374-8
references.pmid: 12613259
references.citation: Genome Biol. 2008 Jan 11;9(1):R7
references.pmid: 18190707
references.citation: Cell. 2015 May 21;161(5):1012-25
references.pmid: 25959774
references.citation: Genesis. 2014 Dec;52(12):952-8
references.pmid: 25394327
references.citation: Science. 2014 Nov 21;346(6212):1004-6
references.pmid: 25414315
references.citation: Cell. 2012 Mar 2;148(5):908-21
references.pmid: 22341456
references.citation: Methods. 2012 Nov;58(3):221-30
references.pmid: 22609568
references.citation: PLoS Genet. 2013;9(12):e1004018
references.pmid: 24385922
references.citation: Bioinformatics. 2007 May 1;23(9):1061-7
references.pmid: 17332020
references.citation: Methods Mol Biol. 2000;132:365-86
references.pmid: 10547847
references.citation: Science. 2002 Feb 15;295(5558):1306-11
references.pmid: 11847345
references.citation: Genome Res. 2012 Aug;22(8):1581-8
references.pmid: 22555592
references.citation: Brief Funct Genomics. 2012 Mar;11(2):177-86
references.pmid: 22441554
references.citation: Nat Struct Mol Biol. 2011 Jan;18(1):107-14
references.pmid: 21131981
references.citation: PLoS Biol. 2012 Jan;10(1):e1001244
references.pmid: 22272186
references.citation: PLoS Biol. 2005 Oct;3(10):e314
references.pmid: 16128622
references.citation: Cell Rep. 2015 Mar 3;10(8):1297-309
references.pmid: 25732821
references.citation: Cell. 2011 Nov 23;147(5):1132-45
references.pmid: 22118467
references.citation: Nature. 2014 Mar 20;507(7492):371-5
references.pmid: 24646999
references.citation: Trends Cell Biol. 2014 Nov;24(11):703-11
references.pmid: 25218583
references.citation: Bioinformatics. 2011 Nov 1;27(21):2957-63
references.pmid: 21903629
references.citation: BMC Bioinformatics. 2005 Feb 15;6:31
references.pmid: 15713233
references.citation: Bioinformatics. 2013 Feb 1;29(3):308-15
references.pmid: 23202746
references.citation: Nat Methods. 2013 Dec;10(12):1213-8
references.pmid: 24097267
references.citation: J Exp Zool B Mol Dev Evol. 2007 Jul 15;308(4):484-93
references.pmid: 17520703
references.citation: Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W273-9
references.pmid: 15215394