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Series GSE153078 Query DataSets for GSE153078
Status Public on Jul 08, 2021
Title A SUMOylation-induced Satb1/Satb2 switch drives embryonic stem cell differentiation [HiC]
Organism Mus musculus
Experiment type Other
Summary The chromatin organizers Satb1 and Satb2 regulate developmental genes in a tissue- and locus-specific manner. In mouse Embryonic Stem Cells (mESCs), the Satb proteins are involved in the balance between pluripotency and differentiation by direct control of key developmental factors such as Nanog and a number of Hox genes. Despite their structural similarities, the Satb proteins regulate mESC pluripotency in opposing ways: Satb1 promotes differentiation by repressing Nanog and activating the neural genes Bcl2 and Nestin, while Satb2 supports the pluripotent state by activating Nanog and repressing Satb1. To further address the mechanisms by which the Satb proteins regulate gene expression, we examined the conjugation of Satb2 with the small ubiquitin-like modifier (SUMO) in pluripotent and differentiated mESCs. We describe for the first time the endogenous SUMOylation of Satb2 in mESCs as a response to developmental cues. We found that Satb2 is progressively SUMO2-modified during differentiation of ESCs towards ectodermal precursors. Moreover, we identified Zfp451 as a SUMO E3 ligase able to interact with and modify Satb2 with SUMO2 in vitro and in vivo. Ablation of Zfp451 or mutation of the SUMO-acceptor lysines in the Satb2 protein disrupt the ability of mESCs to efficiently shut-down pluripotency genes and activate the differentiation program. Importantly, forced expression of SUMO2-Satb2 N-terminal fusions rescues the differentiation defect of SUMO-Satb2 deficient mESCs. Mechanistically, SUMOylation reduces binding of Satb2 to a subset of loci associated to pluripotency genes and changes the composition of Satb2-containing complexes in chromatin. Taken together, our data suggests that SUMO modification of the chromatin organizer Satb2 by the E3 ligase Zfp451 is required for the efficient downregulation of pluripotency genes and initiation of the differentiation program in mouse embryonic stem cells.
 
Overall design HiC during mESC differentiation in neural progenitor conditions, with and without Satb2 K233/350R sumoylation mutant
 
Contributor(s) Urrutia GA, Ramachandran H, Cauchy P, Ramamoorthy S, Thomas C, Sören B, Mittler G, Grosschedl R
Citation(s)
  • Antonio Urrutia G, Ramachandran H, Cauchy P, Boo K et al. ZFP451-mediated SUMOylation of SATB2 drives embryonic stem cell differentiation. Genes Dev 2021 Aug 1;35(15-16):1142-1160. PMID: 34244292
Submission date Jun 23, 2020
Last update date Oct 07, 2021
Contact name Pierre Daniel Cauchy
E-mail(s) cauchy@ie-freiburg.mpg.de
Phone +49 (0)761 270-77576
Organization name University Medical Center Freiburg
Department Zentrum für Translationale Zellforschung
Lab AG Onco-Immunology
Street address Breisacher Str. 115
City Freiburg
State/province Baden-Württemberg
ZIP/Postal code 79106
Country Germany
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (3)
GSM4633883 WT_LIF_d0
GSM4633884 WT_RA_d4
GSM4633885 dm_RA_d4
This SubSeries is part of SuperSeries:
GSE119991 A SUMOylation-induced Satb1/Satb2 switch drives embryonic stem cell differentiation
Relations
BioProject PRJNA641396
SRA SRP268484

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE153078_RAW.tar 259.5 Mb (http)(custom) TAR (of H5)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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