ArticleThe Journal of biological chemistry2013
The epigenetic modifier ubiquitin-specific protease 22 (USP22) regulates embryonic stem cell differentiation via transcriptional repression of sex-determining region Y-box 2 (SOX2).
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism.Nature · 2015Pooled it
- Roles of ubiquitin‑specific peptidase 22 in cellular fate: From embryonic survival to tissue repair, inflammation and metabolism (Review).International journal of molecular medicine · 2026Review
- The Potential Role of Deubiquitinating Enzymes (DUBs) in Male Fertility.Biomolecules · 2026Review
- Signaling pathways as the pivotal regulators of cisplatin resistance in tumor cells through SOX2 upregulation.Medical oncology (Northwood, London, England) · 2025Review
- Key roles of ubiquitination in regulating critical regulators of cancer stem cell functionality.Genes & diseases · 2025Review
- A chromatin-focused CRISPR screen identifies USP22 as a barrier to somatic cell reprogramming.Communications biology · 2025Article
- Ubiquitin-specific peptidase 22 controls integrin-dependent cancer cell stemness and metastasis.iScience · 2024Article
- Genome-wide analysis of genes encoding core components of the ubiquitin system during cerebral cortex development.Molecular brain · 2022Article
- Ubiquitin-specific proteases in inflammatory bowel disease-related signalling pathway regulation.Cell death & disease · 2022Review
- The related coactivator complexes SAGA and ATAC control embryonic stem cell self-renewal through acetyltransferase-independent mechanisms.Cell reports · 2021Article
- USP22 controls necroptosis by regulating receptor-interacting protein kinase 3 ubiquitination.EMBO reports · 2021Article
- Deubiquitylases in developmental ubiquitin signaling and congenital diseases.Cell death and differentiation · 2021Review
- Decitabine and Cisplatin are Synergistic to Exert Anti-Tumor Effect on Gastric Cancer via Inducing Sox2 DNA Demethylation.OncoTargets and therapy · 2021Article
- Histone Monoubiquitination in Chromatin Remodelling: Focus on the Histone H2B Interactome and Cancer.Cancers · 2020Review
- Review
- The inhibitory effect of compound ChlA-F on human bladder cancer cell invasion can be attributed to its blockage of SOX2 protein.Cell death and differentiation · 2020Article
- CAMKV Is a Candidate Immunotherapeutic Target inFrontiers in oncology · 2020Article
- Inhibition of USP2 eliminates cancer stem cells and enhances TNBC responsiveness to chemotherapy.Cell death & disease · 2019Article
- USP22 controls multiple signaling pathways that are essential for vasculature formation in the mouse placenta.Development (Cambridge, England) · 2019Article
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Pluripotent embryonic stem cells (ESCs) undergo self-renewal until stimulated to differentiate along specific lineage pathways. Many of the transcriptional networks that drive reprogramming of a self-renewing ESC to a differentiating cell have been identified. However, fundamental questions remain unanswered about the epigenetic programs that control these changes in gene expression. Here we report that the histone ubiquitin hydrolase ubiquitin-specific protease 22 (USP22) is a critical epigenetic modifier that controls this transition from self-renewal to differentiation. USP22 is induced as ESCs differentiate and is necessary for differentiation into all three germ layers. We further report that USP22 is a transcriptional repressor of the locus encoding the core pluripotency factor sex-determining region Y-box 2 (SOX2) in ESCs, and this repression is required for efficient differentiation. USP22 occupies the Sox2 promoter and hydrolyzes monoubiquitin from ubiquitylated histone H2B and blocks transcription of the Sox2 locus. Our study reveals an epigenetic mechanism that represses the core pluripotency transcriptional network in ESCs, allowing ESCs to transition from a state of self-renewal into lineage-specific differentiation programs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.