Abstract

The nucleosome remodeling and deacetylase (NuRD) complex plays an important role in gene expression regulation, stem cell self-renewal, and lineage commitment. However, little is known about the dynamics of NuRD during cellular differentiation. Here, we study these dynamics using genome-wide profiling and quantitative interaction proteomics in mouse embryonic stem cells (ESCs) and neural progenitor cells (NPCs). We find that the genomic targets of NuRD are highly dynamic during differentiation, with most binding occurring at cell-type specific promoters and enhancers. We identify ZFP296 as an ESC-specific NuRD interactor that also interacts with the SIN3A complex. ChIP-sequencing in Zfp296 knockout (KO) ESCs reveals decreased NuRD binding both genome-wide and at ZFP296 binding sites, although this has little effect on the transcriptome. Nevertheless, Zfp296 KO ESCs exhibit delayed induction of lineage-specific markers upon differentiation to embryoid bodies. In summary, we identify an ESC-specific NuRD-interacting protein which regulates genome-wide NuRD binding and cellular differentiation.

Details

Title
NuRD-interacting protein ZFP296 regulates genome-wide NuRD localization and differentiation of mouse embryonic stem cells
Author
Kloet, Susan L 1   VIAFID ORCID Logo  ; Karemaker, Ino D 2   VIAFID ORCID Logo  ; Lisa van Voorthuijsen 2   VIAFID ORCID Logo  ; Lindeboom, Rik G H 2   VIAFID ORCID Logo  ; Baltissen, Marijke P 2 ; Edupuganti, Raghu R 3 ; Poramba-Liyanage, Deepani W 3   VIAFID ORCID Logo  ; Pascal W T C Jansen 2 ; Vermeulen, Michiel 2   VIAFID ORCID Logo 

 Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, The Netherlands; Leiden Genome Technology Center, Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands 
 Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, Nijmegen, The Netherlands 
 Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, The Netherlands 
Pages
1-11
Publication year
2018
Publication date
Nov 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2128533427
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.