{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T15:31:00Z","timestamp":1770996660016,"version":"3.50.1"},"reference-count":80,"publisher":"Oxford University Press (OUP)","issue":"15","license":[{"start":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T00:00:00Z","timestamp":1593993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010659","name":"Erasmus University Medical Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Polish National Science Centre","doi-asserted-by":"crossref","award":["UMO-2015\/19\/B\/NZ4\/03184"],"award-info":[{"award-number":["UMO-2015\/19\/B\/NZ4\/03184"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The transcription factor zinc finger E-box binding protein 2 (ZEB2) controls embryonic and adult cell fate decisions and cellular maturation in many stem\/progenitor cell types. Defects in these processes in specific cell types underlie several aspects of Mowat\u2013Wilson syndrome (MOWS), which is caused by ZEB2 haplo-insufficiency. Human ZEB2, like mouse Zeb2, is located on chromosome 2 downstream of a \u00b13.5\u00a0Mb-long gene-desert, lacking any protein-coding gene. Using temporal targeted chromatin capture (T2C), we show major chromatin structural changes based on mapping in-cis proximities between the ZEB2 promoter and this gene desert during neural differentiation of human-induced pluripotent stem cells, including at early neuroprogenitor cell (NPC)\/rosette state, where ZEB2 mRNA levels increase significantly. Combining T2C with histone-3 acetylation mapping, we identified three novel candidate enhancers about 500\u00a0kb upstream of the ZEB2 transcription start site. Functional luciferase-based assays in heterologous cells and NPCs reveal co-operation between these three enhancers. This study is the first to document in-cis Regulatory Elements located in ZEB2\u2019s gene desert. The results further show the usability of T2C for future studies of ZEB2 REs in differentiation and maturation of multiple cell types and the molecular characterization of newly identified MOWS patients that lack mutations in ZEB2 protein-coding exons.<\/jats:p>","DOI":"10.1093\/hmg\/ddaa141","type":"journal-article","created":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T19:11:59Z","timestamp":1593717119000},"page":"2535-2550","source":"Crossref","is-referenced-by-count":15,"title":["Targeted chromatin conformation analysis identifies novel distal neural enhancers of ZEB2 in pluripotent stem cell differentiation"],"prefix":"10.1093","volume":"29","author":[{"given":"Judith C","family":"Birkhoff","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Erasmus University Medical Center, Rotterdam, CN 3015, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rutger W W","family":"Brouwer","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Erasmus University Medical Center, Rotterdam, CN 3015, The Netherlands"},{"name":"Center for Biomics, Erasmus University Medical Center, Rotterdam, CN 3015, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petros","family":"Kolovos","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis 68100, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne L","family":"Korporaal","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Erasmus University Medical Center, Rotterdam, CN 3015, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Bermejo-Santos","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Erasmus University Medical Center, Rotterdam, CN 3015, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilias","family":"Boltsis","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Erasmus University Medical Center, Rotterdam, CN 3015, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6000-9387","authenticated-orcid":false,"given":"Karol","family":"Nowosad","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Erasmus University Medical Center, Rotterdam, CN 3015, The Netherlands"},{"name":"Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin 20-093, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirjam C G N","family":"van den Hout","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Erasmus University Medical Center, Rotterdam, CN 3015, The Netherlands"},{"name":"Center for Biomics, Erasmus University Medical Center, Rotterdam, CN 3015, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank G","family":"Grosveld","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Erasmus University Medical Center, Rotterdam, CN 3015, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilfred F J","family":"van IJcken","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Erasmus University Medical Center, Rotterdam, CN 3015, The Netherlands"},{"name":"Center for Biomics, Erasmus University Medical Center, Rotterdam, CN 3015, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danny","family":"Huylebroeck","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Erasmus University Medical Center, Rotterdam, CN 3015, The Netherlands"},{"name":"Department of Development and Regeneration, KU Leuven, Leuven B-3000, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6256-1706","authenticated-orcid":false,"given":"Andrea","family":"Conidi","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Erasmus University Medical Center, Rotterdam, CN 3015, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,7,6]]},"reference":[{"key":"2020090402223023800_ref1","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/nature08451","article-title":"Genomic views of distant-acting enhancers","volume":"461","author":"Visel","year":"2009","journal-title":"Nature"},{"key":"2020090402223023800_ref2","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nature12753","article-title":"Topology of mammalian developmental enhancers and their regulatory 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