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Evolutionary comparison reveals that diverging CTCF sites are signatures of ancestral topological associating domains borders

Gómez-Marín, Carlos and Tena, Juan J. and Acemel, Rafael D. and López-Mayorga, Macarena and Naranjo, Silvia and de la Calle-Mustienes, Elisa and Maeso, Ignacio and Beccari, Leonardo and Aneas, Ivy and Vielmas, Erika and Bovolenta, Paola and Nobrega, Marcelo A. and Carvajal, Jaime and Gómez-Skarmeta, José Luis (2015) Evolutionary comparison reveals that diverging CTCF sites are signatures of ancestral topological associating domains borders. Proceedings of the National Academy of Sciences of the United States of America, 112 (24). pp. 7542-7547. ISSN 0027-8424. PMCID PMC4475986. https://resolver.caltech.edu/CaltechAUTHORS:20150608-132001190

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Abstract

Increasing evidence in the last years indicates that the vast amount of regulatory information contained in mammalian genomes is organized in precise 3D chromatin structures. However, the impact of this spatial chromatin organization on gene expression and its degree of evolutionary conservation is still poorly understood. The Six homeobox genes are essential developmental regulators organized in gene clusters conserved during evolution. Here, we reveal that the Six clusters share a deeply evolutionarily conserved 3D chromatin organization that predates the Cambrian explosion. This chromatin architecture generates two largely independent regulatory landscapes (RLs) contained in two adjacent topological associating domains (TADs). By disrupting the conserved TAD border in one of the zebrafish Six clusters, we demonstrate that this border is critical for preventing competition between promoters and enhancers located in separated RLs, thereby generating different expression patterns in genes located in close genomic proximity. Moreover, evolutionary comparison of Six-associated TAD borders reveals the presence of CCCTC-binding factor (CTCF) sites with diverging orientations in all studied deuterostomes. Genome-wide examination of mammalian HiC data reveals that this conserved CTCF configuration is a general signature of TAD borders, underscoring that common organizational principles underlie TAD compartmentalization in deuterostome evolution.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1073/pnas.1505463112DOIArticle
http://www.pnas.org/content/112/24/7542PublisherArticle
http://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1505463112/-/DCSupplementalPublisherSupporting Information
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4475986/PubMed CentralArticle
Additional Information:© 2015 National Academy of Sciences. Published online before print June 1, 2015. Edited by Denis Duboule, University of Geneva, Geneva, Switzerland, and approved May 7, 2015 (received for review March 18, 2015. We thank Dr. Eric Davidson for support with the sea urchin experiments; Dr. W. De Laat for providing the 4C-seq method before publication; Fernando Casares for fruitful discussions; and Drs. Pascal Maire (Institute of Biomedical Research) and Tristán Rodríguez (Imperial College London) for providing reagents. This study was supported by the Spanish and Andalusian Governments (BFU2013-41322-P and Proyecto de Excelencia BIO-396 to J.L.G.-S., BFU2013-43213-P to P.B., BFU2014-55738-REDT to J.L.G.-S. and P.B., and BFU2011-22928 to J.C. and M.L.-M.). EU-FP7-PEOPLE-2011-CIG Grant 303904 “EPAXIALMYF5KO” also supported J.C. Author contributions: C.G.-M., J.C., and J.L.G.-S. designed research; C.G.-M., R.D.A., M.L.-M., S.N., E.d.l.C.-M., L.B., and E.V. performed research; I.A. and M.A.N. contributed new reagents/analytic tools; C.G.-M. and J.J.T. analyzed data; and I.M., P.B., J.C., and J.L.G.-S. wrote the paper. The authors declare no conflict of interest. This article is a PNAS Direct Submission. Data deposition: The sequence reported in this paper has been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE66900). This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1505463112/-/DCSupplemental.
Funders:
Funding AgencyGrant Number
Spanish and Andalusian GovernmentsBFU2013-41322-P
Spanish and Andalusian Governments Proyecto de ExcelenciaBIO-396
Spanish and Andalusian GovernmentsBFU2013-43213-P
Spanish and Andalusian GovernmentsBFU2014-55738-REDT
Spanish and Andalusian GovernmentsBFU2011-22928
EU-FP7-PEOPLE-2011-CIG303904 EPAXIALMYF5KO
Subject Keywords:CTCF; TAD; Six cluster; regulatory landscapes; evolution
Issue or Number:24
PubMed Central ID:PMC4475986
Record Number:CaltechAUTHORS:20150608-132001190
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150608-132001190
Official Citation:Carlos Gómez-Marín, Juan J. Tena, Rafael D. Acemel, Macarena López-Mayorga, Silvia Naranjo, Elisa de la Calle-Mustienes, Ignacio Maeso, Leonardo Beccari, Ivy Aneas, Erika Vielmas, Paola Bovolenta, Marcelo A. Nobrega, Jaime Carvajal, and José Luis Gómez-Skarmeta Evolutionary comparison reveals that diverging CTCF sites are signatures of ancestral topological associating domains borders PNAS 2015 112 (24) 7542-7547; published ahead of print June 1, 2015, doi:10.1073/pnas.1505463112
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:58086
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:09 Jun 2015 14:03
Last Modified:03 Oct 2019 08:32

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