{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T01:33:00Z","timestamp":1777599180877,"version":"3.51.4"},"reference-count":65,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012352","name":"Universit\u00e0 degli Studi di Milano","doi-asserted-by":"publisher","award":["PSR2018_DIP_013_LINEA 2_2018_SIRCHIA"],"award-info":[{"award-number":["PSR2018_DIP_013_LINEA 2_2018_SIRCHIA"]}],"id":[{"id":"10.13039\/100012352","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Traditionally, Cornelia de Lange Syndrome (CdLS) is considered a cohesinopathy caused by constitutive mutations in cohesin complex genes. Cohesin is a major regulator of chromatin architecture, including the formation of chromatin loops at the imprinted IGF2\/H19 domain. We used 3C analysis on lymphoblastoid cells from CdLS patients carrying mutations in NIPBL and SMC1A genes to explore 3D chromatin structure of the IGF2\/H19\u00a0locus and evaluate the influence of cohesin alterations in chromatin architecture. We also assessed quantitative expression of imprinted loci and WNT pathway genes, together with DMR methylation status of the imprinted genes. A general impairment of chromatin architecture and the emergence of new interactions were found. Moreover, imprinting alterations also involved the expression and methylation levels of imprinted genes, suggesting an association among cohesin genetic defects, chromatin architecture impairment, and imprinting network alteration. The WNT pathway resulted dysregulated: canonical WNT, cell cycle, and WNT signal negative regulation were the most significantly affected subpathways. Among the deregulated pathway nodes, the key node of the frizzled receptors was repressed. Our study provides new evidence that mutations in genes of the cohesin complex have effects on the chromatin architecture and epigenetic stability of genes commonly regulated by high order chromatin structure.<\/jats:p>","DOI":"10.3390\/biom11111622","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T12:39:42Z","timestamp":1635856782000},"page":"1622","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cohesin Mutations Induce Chromatin Conformation Perturbation of the H19\/IGF2 Imprinted Region and Gene Expression Dysregulation in Cornelia de Lange Syndrome Cell Lines"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4306-9476","authenticated-orcid":false,"given":"Silvana","family":"Pileggi","sequence":"first","affiliation":[{"name":"Medical Genetics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1103-6223","authenticated-orcid":false,"given":"Marta","family":"La Vecchia","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9062-3188","authenticated-orcid":false,"given":"Elisa Adele","family":"Colombo","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9517-6997","authenticated-orcid":false,"given":"Laura","family":"Fontana","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milano, Italy"},{"name":"Unit of Medical Genetics, ASST Santi Paolo e Carlo, 20142 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrizia","family":"Colapietro","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, Medical Genetics, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davide","family":"Rovina","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4247-4365","authenticated-orcid":false,"given":"Annamaria","family":"Morotti","sequence":"additional","affiliation":[{"name":"Research Laboratories Coordination Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5260-6691","authenticated-orcid":false,"given":"Silvia","family":"Tabano","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, Medical Genetics, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"},{"name":"Laboratory of Medical Genetics, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Porta","sequence":"additional","affiliation":[{"name":"Centro di Medicina Genomica, Department of Medicine and Surgery, Universit\u00e0 degli Studi dell\u2019Insubria, 21100 Varese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5558-4272","authenticated-orcid":false,"given":"Myriam","family":"Alcalay","sequence":"additional","affiliation":[{"name":"Department of Experimental Oncology, IEO European Institute of Oncology IRCCS, 20139 Milan, Italy"},{"name":"Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1165-7935","authenticated-orcid":false,"given":"Cristina","family":"Gervasini","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Miozzo","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milano, Italy"},{"name":"Unit of Medical Genetics, ASST Santi Paolo e Carlo, 20142 Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6106-3721","authenticated-orcid":false,"given":"Silvia 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