ArticleNature genetics2021
p53 convergently activates Dux/DUX4 in embryonic stem cells and in facioscapulohumeral muscular dystrophy cell models.
Article in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 111 citations in OpenAlex.
- High-throughput functional characterization of enhancers in totipotent-like cells.Nature communications · 2026Article
- Phase separation of DUX family proteins drives totipotent-like state via 3D genome reorganization and retrotransposon activation.Protein & cell · 2026Article
- CtBP1/2 restrict DUX-dependent and independent 2C-like programs in mouse embryonic stem cells.EMBO reports · 2026Article
- mRNA translational dynamics mediates totipotent-like reprogramming.The Journal of biological chemistry · 2026Article
- Alterations in chromatin organization promote totipotent-like features in a DPPA2/DUX-dependent manner.The EMBO journal · 2026Article
- The emergence and diversification of the DUX gene family across placental mammals.Communications biology · 2026Article
- Dynamic regulation of H3K9 dimethylation drives mouse minor zygotic genome activation.Nature structural & molecular biology · 2026Article
- NELFA supports naïve pluripotency and drives 8C-like state in human embryonic stem cells.Nature communications · 2026Article
- Transgenic mouse models for investigating human DUX4 expression during development and its roles in FSHD pathophysiology.Disease models & mechanisms · 2026Article
- Asymmetric division rejuvenates stem cell lineages.Cell research · 2026Article
- Zscan4 enables the formation of the Z compartment.Nature structural & molecular biology · 2026Article
- Z-DNA formation regulates the totipotent-like state and primes Zscan4-dependent chromatin compartmentalization.Nature structural & molecular biology · 2026Article
- Shugoshin 2A stabilizes heterochromatin complexes to suppress the 2-cell-like state in embryonic stem cells.Stem cell reports · 2026Article
- Asymmetric division in a two-cell-like state rejuvenates embryonic stem cells.Cell research · 2026Article
- Chaperonin proteins CCT5 and CCT7 epigenetically restrict the transition from pluripotency to totipotency in embryonic stem cells.Stem cell reports · 2026Article
- Review
- Diversity challenges and reconciles genetics in facioscapulohumeral muscular dystrophy.Journal of human genetics · 2025Review
- DUX4 at 25: how it emerged from "junk DNA" to become the cause of facioscapulohumeral muscular dystrophy.Skeletal muscle · 2025Review
- Ints7 deficiency activates DNA damage response to elicit resurgence of endogenous retrovirus MERVL and anastasis of embryonic stem cells.Nucleic acids research · 2025Article
- USP17L promotes the 2-cell-like program through deubiquitination of H2AK119ub1 and ZSCAN4.Nature communications · 2025Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
In mammalian embryos, proper zygotic genome activation (ZGA) underlies totipotent development. Double homeobox (DUX)-family factors participate in ZGA, and mouse Dux is required for forming cultured two-cell (2C)-like cells. Remarkably, in mouse embryonic stem cells, Dux is activated by the tumor suppressor p53, and Dux expression promotes differentiation into expanded-fate cell types. Long-read sequencing and assembly of the mouse Dux locus reveals its complex chromatin regulation including putative positive and negative feedback loops. We show that the p53-DUX/DUX4 regulatory axis is conserved in humans. Furthermore, we demonstrate that cells derived from patients with facioscapulohumeral muscular dystrophy (FSHD) activate human DUX4 during p53 signaling via a p53-binding site in a primate-specific subtelomeric long terminal repeat (LTR)10C element. In summary, our work shows that p53 activation convergently evolved to couple p53 to Dux/DUX4 activation in embryonic stem cells, embryos and cells from patients with FSHD, potentially uniting the developmental and disease regulation of DUX-family factors and identifying evidence-based therapeutic opportunities for FSHD.
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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.