Deletions of chromosomal regulatory boundaries are associated with congenital disease

Ibn-Salem, Jonas; Köhler, Sebastian; Love, Michael I.; Chung, Ho-Ryun; Huang, Ni; Hurles, Matthew E.; Haendel, Melissa; Washington, Nicole L.; Smedley, Damian; Mungall, Christopher J.; Lewis, Suzanna E.; Ott, Claus-Eric; Bauer, Sebastian; Schofield, Paul N.; Mundlos, Stefan; Spielmann, Malte; Robinson, Peter N.

doi:10.1186/s13059-014-0423-1

Title: Deletions of chromosomal regulatory boundaries are associated with congenital disease

Journal Article · Thu Sep 04 00:00:00 EDT 2014 · Genome Biology (Online)

DOI:https://doi.org/10.1186/s13059-014-0423-1· OSTI ID:1626929

Ibn-Salem, Jonas ^[1]; Köhler, Sebastian ^[2]; Love, Michael I. ^[3]; Chung, Ho-Ryun ^[4]; Huang, Ni ^[5]; Hurles, Matthew E. ^[5]; Haendel, Melissa ^[6]; Washington, Nicole L. ^[7]; Smedley, Damian ^[5]; Mungall, Christopher J. ^[7]; Lewis, Suzanna E. ^[7]; Ott, Claus-Eric ^[4]; Bauer, Sebastian ^[2]; Schofield, Paul N. ^[8]; Mundlos, Stefan ^[9]; Spielmann, Malte ^[10]; Robinson, Peter N. ^[11]

Freie Univ., Berlin (Germany). Dept. of Mathematics and Computer Science; Max Planck Inst. for Molecular Genetics, Berlin (Germany); Charité-Universitätsmedizin Berlin (Germany). Inst. for Medical and Human Genetics
Charité-Universitätsmedizin Berlin (Germany). Inst. for Medical and Human Genetics
Max Planck Inst. for Molecular Genetics, Berlin (Germany); International Max Planck Research School for Computational Biology and Scientific Computing, Berlin (Germany)
Max Planck Inst. for Molecular Genetics, Berlin (Germany)
Wellcome Trust Sanger Inst., Hinxton (United Kingdom)
Oregon Health and Science Univ., Portland, OR (United States). Dept. of Medical Informatics & Clinical Epidemiology
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Genomics Division
The Jackson Lab., Bar Harbor, ME (Untied States); Univ. of Cambridge (United Kingdom). Dept. of Physiology, Development and Neuroscience
Max Planck Inst. for Molecular Genetics, Berlin (Germany); Charité-Universitätsmedizin Berlin (Germany). Inst. for Medical and Human Genetics; Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Berlin (Germany)
Max Planck Inst. for Molecular Genetics, Berlin (Germany); Charité-Universitätsmedizin Berlin (Germany). Inst. for Medical and Human Genetics
Freie Univ., Berlin (Germany). Dept. of Mathematics and Computer Science; Max Planck Inst. for Molecular Genetics, Berlin (Germany); Charité-Universitätsmedizin Berlin (Germany). Inst. for Medical and Human Genetics; International Max Planck Research School for Computational Biology and Scientific Computing, Berlin (Germany); Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Berlin (Germany)

Background: Recent data from genome-wide chromosome conformation capture analysis indicate that the human genome is divided into conserved megabase-sized self-interacting regions called topological domains. These topological domains form the regulatory backbone of the genome and are separated by regulatory boundary elements or barriers. Copy-number variations can potentially alter the topological domain architecture by deleting or duplicating the barriers and thereby allowing enhancers from neighboring domains to ectopically activate genes causing misexpression and disease, a mutational mechanism that has recently been termed enhancer adoption. Results: We use the Human Phenotype Ontology database to relate the phenotypes of 922 deletion cases recorded in the DECIPHER database to monogenic diseases associated with genes in or adjacent to the deletions. We identify combinations of tissue-specific enhancers and genes adjacent to the deletion and associated with phenotypes in the corresponding tissue, whereby the phenotype matched that observed in the deletion. We compare this computationally with a gene-dosage pathomechanism that attempts to explain the deletion phenotype based on haploinsufficiency of genes located within the deletions. Up to 11.8% of the deletions could be best explained by enhancer adoption or a combination of enhancer adoption and gene-dosage effects. Conclusions: Our results suggest that enhancer adoption caused by deletions of regulatory boundaries may contribute to a substantial minority of copy-number variation phenotypes and should thus be taken into account in their medical interpretation.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division; European Community's Seventh Framework Program; National Institutes of Health (NIH)

Grant/Contract Number:: AC02-05CH11231; 602300; 5R24OD011883

OSTI ID:: 1626929

Journal Information:: Genome Biology (Online), Vol. 15, Issue 9; ISSN 1474-760X

Publisher:: BioMed CentralCopyright Statement

Country of Publication:: United States

Language:: English

References (75)

Cohesin and CTCF differentially affect chromatin architecture and gene expression in human cells Zuin, J.; Dixon, J. R.; van der Reijden, M. I. J. A. Proceedings of the National Academy of Sciences, Vol. 111, Issue 3 https://doi.org/10.1073/pnas.1317788111	journal	December 2013
Mapping and analysis of chromatin state dynamics in nine human cell types Ernst, Jason; Kheradpour, Pouya; Mikkelsen, Tarjei S. Nature, Vol. 473, Issue 7345 https://doi.org/10.1038/nature09906	journal	March 2011
Differential DNase I hypersensitivity reveals factor-dependent chromatin dynamics He, Housheng Hansen; Meyer, Clifford A.; Chen, Mei Wei Genome Research, Vol. 22, Issue 6 https://doi.org/10.1101/gr.133280.111	journal	April 2012
Diagnosis of multiple cancer types by shrunken centroids of gene expression Tibshirani, R.; Hastie, T.; Narasimhan, B. Proceedings of the National Academy of Sciences, Vol. 99, Issue 10 https://doi.org/10.1073/pnas.082099299	journal	May 2002
Topology of mammalian developmental enhancers and their regulatory landscapes de Laat, Wouter; Duboule, Denis Nature, Vol. 502, Issue 7472 https://doi.org/10.1038/nature12753	journal	October 2013
DNase-seq: A High-Resolution Technique for Mapping Active Gene Regulatory Elements across the Genome from Mammalian Cells Song, L.; Crawford, G. E. Cold Spring Harbor Protocols, Vol. 2010, Issue 2 https://doi.org/10.1101/pdb.prot5384	journal	February 2010
A microduplication of the long range SHH limb regulator (ZRS) is associated with triphalangeal thumb-polysyndactyly syndrome Klopocki, E.; Ott, C-E; Benatar, N. Journal of Medical Genetics, Vol. 45, Issue 6 https://doi.org/10.1136/jmg.2007.055699	journal	January 2008
The NIH Roadmap Epigenomics Mapping Consortium Bernstein, Bradley E.; Stamatoyannopoulos, John A.; Costello, Joseph F. Nature Biotechnology, Vol. 28, Issue 10 https://doi.org/10.1038/nbt1010-1045	journal	October 2010
Measuring reproducibility of high-throughput experiments Li, Qunhua; Brown, James B.; Huang, Haiyan arXiv https://doi.org/10.48550/arxiv.1110.4705	text	January 2011
A Long ncRNA Links Copy Number Variation to a Polycomb/Trithorax Epigenetic Switch in FSHD Muscular Dystrophy Cabianca, Daphne S.; Casa, Valentina; Bodega, Beatrice Cell, Vol. 149, Issue 4 https://doi.org/10.1016/j.cell.2012.03.035	journal	May 2012
Genes and biological processes commonly disrupted in rare and heterogeneous developmental delay syndromes Shaikh, Tamim H.; Haldeman-Englert, Chad; Geiger, Elizabeth A. Human Molecular Genetics, Vol. 20, Issue 5 https://doi.org/10.1093/hmg/ddq527	journal	December 2010
Multiple-laboratory comparison of microarray platforms Irizarry, Rafael A.; Warren, Daniel; Spencer, Forrest Nature Methods, Vol. 2, Issue 5 https://doi.org/10.1038/nmeth756	journal	April 2005
Phenotype Ontologies and Cross-Species Analysis for Translational Research Robinson, Peter N.; Webber, Caleb PLoS Genetics, Vol. 10, Issue 4 https://doi.org/10.1371/journal.pgen.1004268	journal	April 2014
Characterising and Predicting Haploinsufficiency in the Human Genome Huang, Ni; Lee, Insuk; Marcotte, Edward M. PLoS Genetics, Vol. 6, Issue 10 https://doi.org/10.1371/journal.pgen.1001154	journal	October 2010
ChIP-seq accurately predicts tissue-specific activity of enhancers Visel, Axel; Blow, Matthew J.; Li, Zirong Nature, Vol. 457, Issue 7231 https://doi.org/10.1038/nature07730	journal	February 2009
The core FOXG1 syndrome phenotype consists of postnatal microcephaly, severe mental retardation, absent language, dyskinesia, and corpus callosum hypogenesis Kortüm, F.; Das, S.; Flindt, M. BMJ Publishing Group https://doi.org/10.5167/uzh-47844	text	January 2011
14q12 and severe Rett-like phenotypes: new clinical insights and physical mapping of FOXG1-regulatory elements Allou, Lila; Lambert, Laetitia; Amsallem, Daniel European Journal of Human Genetics, Vol. 20, Issue 12 https://doi.org/10.1038/ejhg.2012.127	journal	June 2012
Williams-Beuren Syndrome Menegazzi, James J. Science, Vol. 311, Issue 5767 https://doi.org/10.1126/science.311.5767.1552c	journal	March 2006
The Antley-Bixler syndrome: Report of two familial cases with severe renal and anal anomalies LeHeup, B. P.; Masutti, J. P.; Droullé, P. European Journal of Pediatrics, Vol. 154, Issue 2 https://doi.org/10.1007/BF01991916	journal	February 1995
The elastin gene is disrupted by a translocation associated with supravalvular aortic stenosis Curran, M. Cell, Vol. 73, Issue 1 https://doi.org/10.1016/0092-8674(93)90168-P	journal	April 1993
Role of fibroblast growth factor receptor signaling in kidney development Bates, Carlton M. American Journal of Physiology-Renal Physiology, Vol. 301, Issue 2 https://doi.org/10.1152/ajprenal.00186.2011	journal	August 2011
Pitx1 haploinsufficiency causes clubfoot in humans and a clubfoot-like phenotype in mice Alvarado, D. M.; McCall, K.; Aferol, H. Human Molecular Genetics, Vol. 20, Issue 20 https://doi.org/10.1093/hmg/ddr313	journal	July 2011
Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome Lieberman-Aiden, E.; van Berkum, N. L.; Williams, L. Science, Vol. 326, Issue 5950 https://doi.org/10.1126/science.1181369	journal	October 2009
An integrated encyclopedia of DNA elements in the human genome Nature, Vol. 489, Issue 7414, p. 57-74 https://doi.org/10.1038/nature11247	journal	September 2012
DECIPHER: web-based, community resource for clinical interpretation of rare variants in developmental disorders Swaminathan, G. J.; Bragin, E.; Chatzimichali, E. A. Human Molecular Genetics, Vol. 21, Issue R1 https://doi.org/10.1093/hmg/dds362	journal	September 2012
Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data Dekker, Job; Marti-Renom, Marc A.; Mirny, Leonid A. Nature Reviews Genetics, Vol. 14, Issue 6 https://doi.org/10.1038/nrg3454	journal	May 2013
Large-scale objective association of mouse phenotypes with human symptoms through structural variation identified in patients with developmental disorders Boulding, Hannah; Webber, Caleb Human Mutation, Vol. 33, Issue 5 https://doi.org/10.1002/humu.22069	journal	April 2012
Semantic Similarity in a Taxonomy: An Information-Based Measure and its Application to Problems of Ambiguity in Natural Language Resnik, P. Journal of Artificial Intelligence Research, Vol. 11 https://doi.org/10.1613/jair.514	journal	July 1999
Chromosome organization: new facts, new models Branco, Miguel R.; Pombo, Ana Trends in Cell Biology, Vol. 17, Issue 3 https://doi.org/10.1016/j.tcb.2006.12.006	journal	March 2007
Measuring reproducibility of high-throughput experiments Li, Qunhua; Brown, James B.; Huang, Haiyan The Annals of Applied Statistics, Vol. 5, Issue 3 https://doi.org/10.1214/11-AOAS466	journal	September 2011
Williams–Beuren Syndrome New England Journal of Medicine, Vol. 362, Issue 22, p. 2142-2142 https://doi.org/10.1056/nejmx100026	journal	June 2010
Microhomology-Mediated Mechanisms Underlie Non-Recurrent Disease-Causing Microdeletions of the FOXL2 Gene or Its Regulatory Domain Verdin, Hannah; D'haene, Barbara; Beysen, Diane PLoS Genetics, Vol. 9, Issue 3 https://doi.org/10.1371/journal.pgen.1003358	journal	March 2013
VISTA Enhancer Browser--a database of tissue-specific human enhancers Visel, A.; Minovitsky, S.; Dubchak, I. Nucleic Acids Research, Vol. 35, Issue Database https://doi.org/10.1093/nar/gkl822	journal	January 2007
Chromatin insulators and long-distance interactions in Drosophila Kyrchanova, Olga; Georgiev, Pavel FEBS Letters, Vol. 588, Issue 1 https://doi.org/10.1016/j.febslet.2013.10.039	journal	November 2013
Asymmetric Lower-Limb Malformations in Individuals with Homeobox PITX1 Gene Mutation Gurnett, Christina A.; Alaee, Farhang; Kruse, Lisa M. The American Journal of Human Genetics, Vol. 83, Issue 5 https://doi.org/10.1016/j.ajhg.2008.10.004	journal	November 2008
Williams-Beuren syndrome None, None Dictionary of Rheumatology https://doi.org/10.1007/978-3-211-79280-3_1166	reference-book	January 2009
Insulators, Not Polycomb Response Elements, Are Required for Long-Range Interactions between Polycomb Targets in Drosophila melanogaster Li, H. -B.; Muller, M.; Bahechar, I. A. Molecular and Cellular Biology, Vol. 31, Issue 4 https://doi.org/10.1128/MCB.00849-10	journal	December 2010
The core FOXG1 syndrome phenotype consists of postnatal microcephaly, severe mental retardation, absent language, dyskinesia, and corpus callosum hypogenesis Kortum, F.; Das, S.; Flindt, M. Journal of Medical Genetics, Vol. 48, Issue 6 https://doi.org/10.1136/jmg.2010.087528	journal	March 2011
Microduplications upstream of MSX2 are associated with a phenocopy of cleidocranial dysplasia Ott, Claus Eric; Hein, Hendrikje; Lohan, Silke Journal of Medical Genetics, Vol. 49, Issue 7 https://doi.org/10.1136/jmedgenet-2012-100825	journal	June 2012
Role of fibroblast growth factor receptor signaling in kidney development Bates, Carlton M. Pediatric Nephrology, Vol. 26, Issue 9 https://doi.org/10.1007/s00467-010-1747-z	journal	September 2011
High-Resolution Mapping and Characterization of Open Chromatin across the Genome Boyle, Alan P.; Davis, Sean; Shulha, Hennady P. Cell, Vol. 132, Issue 2 https://doi.org/10.1016/j.cell.2007.12.014	journal	January 2008
Wnt/β-catenin signaling suppresses DUX4 expression and prevents apoptosis of FSHD muscle cells Block, Gregory J.; Narayanan, Divya; Amell, Amanda M. Human Molecular Genetics, Vol. 22, Issue 23 https://doi.org/10.1093/hmg/ddt314	journal	July 2013
Accurate Distinction of Pathogenic from Benign CNVs in Mental Retardation Hehir-Kwa, Jayne Y.; Wieskamp, Nienke; Webber, Caleb PLoS Computational Biology, Vol. 6, Issue 4 https://doi.org/10.1371/journal.pcbi.1000752	journal	April 2010
Novel cystogenic role of basic fibroblast growth factor in developing rodent kidneys Li, Zhuangwu; Jerebtsova, Marina; Liu, Xue-Hui American Journal of Physiology-Renal Physiology, Vol. 291, Issue 2 https://doi.org/10.1152/ajprenal.00382.2005	journal	August 2006
Clinical Significance of De Novo and Inherited Copy-Number Variation Vulto-van Silfhout, Anneke T.; Hehir-Kwa, Jayne Y.; van Bon, Bregje W. M. Human Mutation, Vol. 34, Issue 12 https://doi.org/10.1002/humu.22442	journal	October 2013
Construction and accessibility of a cross-species phenotype ontology along with gene annotations for biomedical research Köhler, Sebastian; Doelken, Sandra C.; Ruef, Barbara J. F1000Research, Vol. 2 https://doi.org/10.12688/f1000research.2-30.v1	journal	January 2013
Construction and accessibility of a cross-species phenotype ontology along with gene annotations for biomedical research Köhler, Sebastian; Doelken, Sandra C.; Ruef, Barbara J. F1000Research, Vol. 2 https://doi.org/10.12688/f1000research.2-30.v2	journal	January 2013
Homeotic Arm-to-Leg Transformation Associated with Genomic Rearrangements at the PITX1 Locus Spielmann, Malte; Brancati, Francesco; Krawitz, Peter M. The American Journal of Human Genetics, Vol. 91, Issue 4 https://doi.org/10.1016/j.ajhg.2012.08.014	journal	October 2012
LIM-kinase1 Hemizygosity Implicated in Impaired Visuospatial Constructive Cognition Frangiskakis, J. Michael; Ewart, Amanda K.; Morris, Colleen A. Cell, Vol. 86, Issue 1 https://doi.org/10.1016/S0092-8674(00)80077-X	journal	July 1996
Facioscapulohumeral Dystrophy: Incomplete Suppression of a Retrotransposed Gene Snider, Lauren; Geng, Linda N.; Lemmers, Richard J. L. F. PLoS Genetics, Vol. 6, Issue 10 https://doi.org/10.1371/journal.pgen.1001181	journal	October 2010
Identification and Characterization of Cell Type–Specific and Ubiquitous Chromatin Regulatory Structures in the Human Genome Xi, Hualin; Shulha, Hennady P.; Lin, Jane M. PLoS Genetics, Vol. 3, Issue 8 https://doi.org/10.1371/journal.pgen.0030136	journal	August 2007
FOXG1 Is Responsible for the Congenital Variant of Rett Syndrome Ariani, Francesca; Hayek, Giuseppe; Rondinella, Dalila The American Journal of Human Genetics, Vol. 83, Issue 1 https://doi.org/10.1016/j.ajhg.2008.05.015	journal	July 2008
Lacrimo-auriculo-dento-digital (LADD) syndrome with renal and foot anomalies Roodhooft, A. M.; Brussaard, C. C.; Elst, E. Clinical Genetics, Vol. 38, Issue 3 https://doi.org/10.1111/j.1399-0004.1990.tb03574.x	journal	September 1990
14q12 microdeletions excluding FOXG1 give rise to a congenital variant Rett syndrome-like phenotype Ellaway, Carolyn J.; Ho, Gladys; Bettella, Elisa European Journal of Human Genetics, Vol. 21, Issue 5 https://doi.org/10.1038/ejhg.2012.208	journal	September 2012
The UCSC Genome Browser Database: update 2006 Hinrichs, A. S. Nucleic Acids Research, Vol. 34, Issue 90001 https://doi.org/10.1093/nar/gkj144	journal	January 2006
Identification and characterization of cell type-specific and ubiquitous chromatin regulatory structures in the human genome Xi, Hualin; Shulha, Hennady P.; Lin, Jane M. PLoS Genetics, Vol. preprint, Issue 2007 https://doi.org/10.1371/journal.pgen.0030136.eor	journal	January 2005
The UCSC Genome Browser database: 2014 update Karolchik, Donna; Barber, Galt P.; Casper, Jonathan Nucleic Acids Research, Vol. 42, Issue D1 https://doi.org/10.1093/nar/gkt1168	journal	November 2013
Open chromatin defined by DNaseI and FAIRE identifies regulatory elements that shape cell-type identity D., Winter,; T., Wang,; C., Sheffield, N. The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/16t4-7f35	text	January 2011
Topological domains in mammalian genomes identified by analysis of chromatin interactions Dixon, Jesse R.; Selvaraj, Siddarth; Yue, Feng Nature, Vol. 485, Issue 7398 https://doi.org/10.1038/nature11082	journal	April 2012
Pairing between gypsy Insulators Facilitates the Enhancer Action in trans throughout the Drosophila Genome Kravchenko, Elena; Savitskaya, Ekaterina; Kravchuk, Oksana Molecular and Cellular Biology, Vol. 25, Issue 21 https://doi.org/10.1128/MCB.25.21.9283-9291.2005	journal	November 2005
An integrated encyclopedia of DNA elements in the human genome Libraries, The University of North Carolina at Chapel Hill University The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/wcvb-k036	text	January 2012
Enhancer-adoption as a mechanism of human developmental disease Lettice, Laura A.; Daniels, Sarah; Sweeney, Elizabeth Human Mutation, Vol. 32, Issue 12 https://doi.org/10.1002/humu.21615	journal	October 2011
Phenotypic overlap in the contribution of individual genes to CNV pathogenicity revealed by cross-species computational analysis of single-gene mutations in humans, mice and zebrafish Doelken, S. C.; Kohler, S.; Mungall, C. J. Disease Models & Mechanisms, Vol. 6, Issue 2 https://doi.org/10.1242/dmm.010322	journal	October 2012
BEDTools: a flexible suite of utilities for comparing genomic features Quinlan, Aaron R.; Hall, Ira M. Bioinformatics, Vol. 26, Issue 6 https://doi.org/10.1093/bioinformatics/btq033	journal	January 2010
Williams–Beuren Syndrome Pober, Barbara R. New England Journal of Medicine, Vol. 362, Issue 3 https://doi.org/10.1056/NEJMra0903074	journal	January 2010
Structural variations, the regulatory landscape of the genome and their alteration in human disease: Prospects & Overviews Spielmann, Malte; Mundlos, Stefan BioEssays, Vol. 35, Issue 6 https://doi.org/10.1002/bies.201200178	journal	April 2013
Semantic Similarity in a Taxonomy: An Information-Based Measure and its Application to Problems of Ambiguity in Natural Language Resnik, P. arXiv https://doi.org/10.48550/arxiv.1105.5444	text	January 2011
Open chromatin defined by DNaseI and FAIRE identifies regulatory elements that shape cell-type identity Song, L.; Zhang, Z.; Grasfeder, L. L. Genome Research, Vol. 21, Issue 10 https://doi.org/10.1101/gr.121541.111	journal	July 2011
Identical cells with different 3D genomes; cause and consequences? Krijger, Peter HL; de Laat, Wouter Current Opinion in Genetics & Development, Vol. 23, Issue 2 https://doi.org/10.1016/j.gde.2012.12.010	journal	April 2013
The core FOXG1 syndrome phenotype consists of postnatal microcephaly, severe mental retardation, absent language, dyskinesia, and corpus callosum hypogenesis Kortüm, Fanny; Das, Soma; Flindt, Max Universität Regensburg https://doi.org/10.5283/epub.36121	text	January 2011
The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data Köhler, Sebastian; Doelken, Sandra C.; Mungall, Christopher J. Nucleic Acids Research, Vol. 42, Issue D1 https://doi.org/10.1093/nar/gkt1026	journal	November 2013
GTF2I hemizygosity implicated in mental retardation in Williams syndrome: Genotype-phenotype analysis of five families with deletions in the Williams syndrome region Morris, Colleen A.; Mervis, Carolyn B.; Hobart, Holly H. American Journal of Medical Genetics, Vol. 123A, Issue 1 https://doi.org/10.1002/ajmg.a.20496	journal	October 2003
Looping and Interaction between Hypersensitive Sites in the Active β-globin Locus Tolhuis, Bas; Palstra, Robert-Jan; Splinter, Erik Molecular Cell, Vol. 10, Issue 6 https://doi.org/10.1016/S1097-2765(02)00781-5	journal	December 2002
Systematic Localization of Common Disease-Associated Variation in Regulatory DNA Maurano, M. T.; Humbert, R.; Rynes, E. Science, Vol. 337, Issue 6099 https://doi.org/10.1126/science.1222794	journal	September 2012
The bicoid-related homeoprotein Ptx1 defines the most anterior domain of the embryo and differentiates posterior from anterior lateral mesoderm Lanctot, C.; Lamolet, B.; Drouin, J. Development, Vol. 124, Issue 14 https://doi.org/10.1242/dev.124.14.2807	journal	July 1997

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The distributions of protein coding genes within chromatin domains in relation to human disease Muro, Enrique M.; Ibn-Salem, Jonas; Andrade-Navarro, Miguel A. Epigenetics & Chromatin, Vol. 12, Issue 1 https://doi.org/10.1186/s13072-019-0317-2	journal	December 2019
Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells Zhang, Yanxiao; Li, Ting; Preissl, Sebastian Nature Genetics, Vol. 51, Issue 9 https://doi.org/10.1038/s41588-019-0479-7	journal	August 2019
The role of 3D genome organization in development and cell differentiation Zheng, Hui; Xie, Wei Nature Reviews Molecular Cell Biology, Vol. 20, Issue 9 https://doi.org/10.1038/s41580-019-0132-4	journal	June 2019
Spatial Organization of the Nucleus Compartmentalizes and Regulates the Genome Robson, Michael I.; Rizzotto, Andrea; Schirmer, Eric C. Nuclear Pore Complexes in Genome Organization, Function and Maintenance https://doi.org/10.1007/978-3-319-71614-5_1	book	January 2018
Chromatin features constrain structural variation across evolutionary timescales Fudenberg, Geoff; Pollard, Katherine S. Proceedings of the National Academy of Sciences, Vol. 116, Issue 6 https://doi.org/10.1073/pnas.1808631116	journal	January 2019
Clustered CTCF binding is an evolutionary mechanism to maintain topologically associating domains Kentepozidou, Elissavet; Aitken, Sarah J.; Feig, Christine Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.53428	text	January 2020
ClinTAD: a tool for copy number variant interpretation in the context of topologically associated domains Spector, Jacob D.; Wiita, Arun P. Journal of Human Genetics, Vol. 64, Issue 5 https://doi.org/10.1038/s10038-019-0573-9	journal	February 2019
CRISPR-mediated deletion of prostate cancer risk-associated CTCF loop anchors identifies repressive chromatin loops Guo, Yu; Perez, Andrew A.; Hazelett, Dennis J. Genome Biology, Vol. 19, Issue 1 https://doi.org/10.1186/s13059-018-1531-0	journal	October 2018
3D genomics imposes evolution of the domain model of eukaryotic genome organization Razin, Sergey V.; Vassetzky, Yegor S. Chromosoma, Vol. 126, Issue 1 https://doi.org/10.1007/s00412-016-0604-7	journal	June 2016
Crossed wires: 3D genome misfolding in human disease Norton, Heidi K.; Phillips-Cremins, Jennifer E. Journal of Cell Biology, Vol. 216, Issue 11 https://doi.org/10.1083/jcb.201611001	journal	August 2017
Facultative CTCF sites moderate mammary super-enhancer activity and regulate juxtaposed gene in non-mammary cells Willi, M.; Yoo, K. H.; Reinisch, F. Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/ncomms16069	journal	July 2017
Chromatin features constrain structural variation across evolutionary timescales Fudenberg, Geoff; Pollard, Katherine S. bioRxiv https://doi.org/10.1101/285205	posted_content	January 2018

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