Next Article in Journal
Genetic Diversity in the mtDNA of Physarum polycephalum
Next Article in Special Issue
High Performance of a Dominant/X-Linked Gene Panel in Patients with Neurodevelopmental Disorders
Previous Article in Journal
Evaluation of a Less Invasive Cochlear Implant Surgery in OPA1 Mutations Provoking Deafblindness
Previous Article in Special Issue
Haploinsufficiency as a Foreground Pathomechanism of Poirer-Bienvenu Syndrome and Novel Insights Underlying the Phenotypic Continuum of CSNK2B-Associated Disorders
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Genes
Volume 14
Issue 3
10.3390/genes14030629
genes-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Zeb2 DNA-Binding Sites in Neuroprogenitor Cells Reveal Autoregulation and Affirm Neurodevelopmental Defects, Including in Mowat-Wilson Syndrome

by
Judith C. Birkhoff
1,†,
Anne L. Korporaal
1,
Rutger W. W. Brouwer
2,†,
Karol Nowosad
1,3,4,†,
Claudia Milazzo
1,†,
Lidia Mouratidou
1,
Mirjam C. G. N. van den Hout
2,
Wilfred F. J. van IJcken
1,2,
Danny Huylebroeck
1,5,‡ and
Andrea Conidi
1,*,‡
1
Department of Cell Biology, Erasmus University Medical Center, 3015 Rotterdam, The Netherlands
2
Center for Biomics-Genomics, Erasmus University Medical Center, 3015 Rotterdam, The Netherlands
3
Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin, Poland
4
The Postgraduate School of Molecular Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland
5
Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium
*
Author to whom correspondence should be addressed.
†
Current address: J.C.B.: Institute of Translational Stem Cell Research, Helmholtz Munich, 85764 Neuherberg, Germany; K.N.: Genome Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany; R.W.W.B.: Future Facts, 1013 Amsterdam, The Netherlands; C.M.: Department Neuroscience, Erasmus University Medical Center, 3015 Rotterdam, The Netherlands; L.M.: First Department of Psychiatry, Medical School, National and Kapodistrian University of Athens, 157 72 Athens, Greece, and University Mental Health, Neurosciences and Precision Medicine Research Institute “Costas Stefanis”, 115 27 Athens, Greece; A.C.: Cergentis B.V., 3584 Utrecht, The Netherlands, andrea.conidi@cergentis.com.
‡
Shared senior authors.
Genes 2023, 14(3), 629; https://doi.org/10.3390/genes14030629
Submission received: 20 January 2023 / Revised: 16 February 2023 / Accepted: 27 February 2023 / Published: 2 March 2023
(This article belongs to the Special Issue Molecular Mechanisms in Neurodevelopmental Disorders)
Browse Figures
Versions Notes

Abstract

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’s 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.
Keywords: chromatin immunoprecipitation sequencing; embryonic stem cells; Mowat-Wilson syndrome; neural differentiation; neurodevelopmental disorder; syndromes; target genes; transcription factor; transcriptomics; Zeb2 chromatin immunoprecipitation sequencing; embryonic stem cells; Mowat-Wilson syndrome; neural differentiation; neurodevelopmental disorder; syndromes; target genes; transcription factor; transcriptomics; Zeb2

Share and Cite

MDPI and ACS Style

Birkhoff, J.C.; Korporaal, A.L.; Brouwer, R.W.W.; Nowosad, K.; Milazzo, C.; Mouratidou, L.; van den Hout, M.C.G.N.; van IJcken, W.F.J.; Huylebroeck, D.; Conidi, A. Zeb2 DNA-Binding Sites in Neuroprogenitor Cells Reveal Autoregulation and Affirm Neurodevelopmental Defects, Including in Mowat-Wilson Syndrome. Genes 2023, 14, 629. https://doi.org/10.3390/genes14030629

AMA Style

Birkhoff JC, Korporaal AL, Brouwer RWW, Nowosad K, Milazzo C, Mouratidou L, van den Hout MCGN, van IJcken WFJ, Huylebroeck D, Conidi A. Zeb2 DNA-Binding Sites in Neuroprogenitor Cells Reveal Autoregulation and Affirm Neurodevelopmental Defects, Including in Mowat-Wilson Syndrome. Genes. 2023; 14(3):629. https://doi.org/10.3390/genes14030629

Chicago/Turabian Style

Birkhoff, Judith C., Anne L. Korporaal, Rutger W. W. Brouwer, Karol Nowosad, Claudia Milazzo, Lidia Mouratidou, Mirjam C. G. N. van den Hout, Wilfred F. J. van IJcken, Danny Huylebroeck, and Andrea Conidi. 2023. "Zeb2 DNA-Binding Sites in Neuroprogenitor Cells Reveal Autoregulation and Affirm Neurodevelopmental Defects, Including in Mowat-Wilson Syndrome" Genes 14, no. 3: 629. https://doi.org/10.3390/genes14030629

APA Style

Birkhoff, J. C., Korporaal, A. L., Brouwer, R. W. W., Nowosad, K., Milazzo, C., Mouratidou, L., van den Hout, M. C. G. N., van IJcken, W. F. J., Huylebroeck, D., & Conidi, A. (2023). Zeb2 DNA-Binding Sites in Neuroprogenitor Cells Reveal Autoregulation and Affirm Neurodevelopmental Defects, Including in Mowat-Wilson Syndrome. Genes, 14(3), 629. https://doi.org/10.3390/genes14030629

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop