{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T04:16:16Z","timestamp":1778732176664,"version":"3.51.4"},"reference-count":106,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T00:00:00Z","timestamp":1677715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Erasmus University Medical Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Functional perturbation and action mechanism studies have shown that the transcription factor Zeb2 controls cell fate decisions, differentiation, and\/or maturation in multiple cell lineages in embryos and after birth. In cultured embryonic stem cells (ESCs), Zeb2\u2019s mRNA\/protein upregulation is necessary for the exit from primed pluripotency and for entering general and neural differentiation. We edited mouse ESCs to produce Flag-V5 epitope-tagged Zeb2 protein from one endogenous allele. Using chromatin immunoprecipitation coupled with sequencing (ChIP-seq), we mapped 2432 DNA-binding sites for this tagged Zeb2 in ESC-derived neuroprogenitor cells (NPCs). A new, major binding site maps promoter-proximal to Zeb2 itself. The homozygous deletion of this site demonstrates that autoregulation of Zeb2 is necessary to elicit the appropriate Zeb2-dependent effects in ESC-to-NPC differentiation. We have also cross-referenced all the mapped Zeb2 binding sites with previously obtained transcriptome data from Zeb2 perturbations in ESC-derived NPCs, GABAergic interneurons from the ventral forebrain of mouse embryos, and stem\/progenitor cells from the post-natal ventricular-subventricular zone (V-SVZ) in mouse forebrain, respectively. Despite the different characteristics of each of these neurogenic systems, we found interesting target gene overlaps. In addition, our study also contributes to explaining developmental disorders, including Mowat-Wilson syndrome caused by ZEB2 deficiency, and also other monogenic syndromes.<\/jats:p>","DOI":"10.3390\/genes14030629","type":"journal-article","created":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T02:27:25Z","timestamp":1677810445000},"page":"629","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Zeb2 DNA-Binding Sites in Neuroprogenitor Cells Reveal Autoregulation and Affirm Neurodevelopmental Defects, Including in Mowat-Wilson Syndrome"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1133-7915","authenticated-orcid":false,"given":"Judith C.","family":"Birkhoff","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Erasmus University Medical Center, 3015 Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne L.","family":"Korporaal","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Erasmus University Medical Center, 3015 Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7524-6230","authenticated-orcid":false,"given":"Rutger W. W.","family":"Brouwer","sequence":"additional","affiliation":[{"name":"Center for Biomics-Genomics, Erasmus University Medical Center, 3015 Rotterdam, 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, 3015 Rotterdam, The Netherlands"},{"name":"Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin, Poland"},{"name":"The Postgraduate School of Molecular Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Milazzo","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Erasmus University Medical Center, 3015 Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lidia","family":"Mouratidou","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Erasmus University Medical Center, 3015 Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2412-7631","authenticated-orcid":false,"given":"Mirjam C. G. N.","family":"van den Hout","sequence":"additional","affiliation":[{"name":"Center for Biomics-Genomics, Erasmus University Medical Center, 3015 Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0421-8301","authenticated-orcid":false,"given":"Wilfred F. J.","family":"van IJcken","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Erasmus University Medical Center, 3015 Rotterdam, The Netherlands"},{"name":"Center for Biomics-Genomics, Erasmus University Medical Center, 3015 Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4862-1079","authenticated-orcid":false,"given":"Danny","family":"Huylebroeck","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Erasmus University Medical Center, 3015 Rotterdam, The Netherlands"},{"name":"Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Conidi","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Erasmus University Medical Center, 3015 Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3543","DOI":"10.1093\/nar\/19.13.3543","article-title":"Identification of nuclear factor delta EF1 and its binding site essential for lens-specific activity of the delta 1-crystallin enhancer","volume":"19","author":"Funahashi","year":"1991","journal-title":"Nucleic Acids Res."},{"key":"ref_2","first-page":"5692","article-title":"The delta-crystallin enhancer-binding protein delta EF1 is a repressor of E2-box-mediated gene activation","volume":"14","author":"Sekido","year":"1994","journal-title":"Mol. 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