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Status |
Public on Jul 08, 2021 |
Title |
A SUMOylation-induced Satb1/Satb2 switch drives embryonic stem cell differentiation [ChIP-Seq] |
Organism |
Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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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.
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Overall design |
ChIP-Seq for Satb2, Satb1, and LSD1 during mESC differentiation in neural progenitor conditions, with and without Satb2 K233/350R sumoylation mutant
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Contributor(s) |
Antonio Urrutia G, Ramachandran H, Cauchy P, Ramamoorthy S, Dogan E, Mittler G, Pichler A, Grosschedl R |
Citation(s) |
34244292 |
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Submission date |
Sep 14, 2018 |
Last update date |
Oct 07, 2021 |
Contact name |
Pierre Daniel Cauchy |
E-mail(s) |
cauchy@ie-freiburg.mpg.de
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Phone |
+49 (0)761 270-77576
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Organization name |
University Medical Center Freiburg
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Department |
Zentrum für Translationale Zellforschung
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Lab |
AG Onco-Immunology
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Street address |
Breisacher Str. 115
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City |
Freiburg |
State/province |
Baden-Württemberg |
ZIP/Postal code |
79106 |
Country |
Germany |
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Platforms (1) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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Samples (32)
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This SubSeries is part of SuperSeries: |
GSE119991 |
A SUMOylation-induced Satb1/Satb2 switch drives embryonic stem cell differentiation |
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Relations |
BioProject |
PRJNA490901 |
SRA |
SRP161789 |