ArticleGenes & development2015
Terminal epidermal differentiation is regulated by the interaction of Fra-2/AP-1 with Ezh2 and ERK1/2.
Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 50 citations in OpenAlex.
- HPV8-E6 drives coordinated transcriptional and epigenetic reprogramming of keratinocytes.Tumour virus research · 2026Article
- The promoting roles of GLP1R and GIPR in stemness maintenance and multiple lineage-specific differentiation of PDLSCs.Cellular & molecular biology letters · 2026Article
- Unraveling the Mechanisms Involved in the Beneficial Effects of Magnesium Treatment on Skin Wound Healing.International journal of molecular sciences · 2024Article
- Roles of Glutathione and AP-1 in the Enhancement of Vitamin D-Induced Differentiation by Activators of the Nrf2 Signaling Pathway in Acute Myeloid Leukemia Cells.International journal of molecular sciences · 2024Article
- Kaposi's Sarcoma-Associated Herpesvirus Immediate Early Proteins Trigger FOXQ1 Expression in Oral Epithelial Cells, Engaging in a Novel Lytic Cycle-Sustaining Positive Feedback Loop.Journal of virology · 2023Article
- Protection of c-Fos from autophagic degradation by PRMT1-mediated methylation fosters gastric tumorigenesis.International journal of biological sciences · 2023Article
- Article
- HiCuT: An efficient and low input method to identify protein-directed chromatin interactions.PLoS genetics · 2022Article
- SNAI2 is induced by transforming growth factor-β1, but is not essential for epithelial-mesenchymal transition in human keratinocyte HaCaT cells.Experimental and therapeutic medicine · 2021Article
- Exploring the dermotoxicity of the mycotoxin deoxynivalenol: combined morphologic and proteomic profiling of human epidermal cells reveals alteration of lipid biosynthesis machinery and membrane structural integrity relevant for skin barrier function.Archives of toxicology · 2021Article
- Noncanonical Functions of the Polycomb Group Protein EZH2 in Breast Cancer.The American journal of pathology · 2021Review
- Transcriptional and signalling regulation of skin epithelial stem cells in homeostasis, wounds and cancer.Experimental dermatology · 2021Review
- Review
- SPT6 promotes epidermal differentiation and blockade of an intestinal-like phenotype through control of transcriptional elongation.Nature communications · 2021Article
- Single-Cell Sequencing Reveals the Novel Role of Ezh2 in NK Cell Maturation and Function.Frontiers in immunology · 2021Article
- The CDK4/6-EZH2 pathway is a potential therapeutic target for psoriasis.The Journal of clinical investigation · 2020Article
- Age-of-onset information helps identify 76 genetic variants associated with allergic disease.PLoS genetics · 2020Article
- Functional interactions between Mi-2β and AP1 complexes control response and recovery from skin barrier disruption.The Journal of experimental medicine · 2020Article
- SOX11 and SOX4 drive the reactivation of an embryonic gene program during murine wound repair.Nature communications · 2019Article
- Jarid1b promotes epidermal differentiation by mediating the repression of Ship1 and activation of the AKT/Ovol1 pathway.Cell proliferation · 2019Article
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Authors and funding
8 authors at 3 institutions in 4 countries.
Funding
Abstract
Altered epidermal differentiation characterizes numerous skin diseases affecting >25% of the human population. Here we identified Fra-2/AP-1 as a key regulator of terminal epidermal differentiation. Epithelial-restricted, ectopic expression of Fra-2 induced expression of epidermal differentiation genes located within the epidermal differentiation complex (EDC). Moreover, in a papilloma-prone background, a reduced tumor burden was observed due to precocious keratinocyte differentiation by Fra-2 expression. Importantly, loss of Fra-2 in suprabasal keratinocytes is sufficient to cause skin barrier defects due to reduced expression of differentiation genes. Mechanistically, Fra-2 binds and transcriptionally regulates EDC gene promoters, which are co-occupied by the transcriptional repressor Ezh2. Fra-2 remains transcriptionally inactive in nondifferentiated keratinocytes, where it was found monomethylated and dimethylated on Lys104 and interacted with Ezh2. Upon keratinocyte differentiation, Fra-2 is C-terminally phosphorylated on Ser320 and Thr322 by ERK1/2, leading to transcriptional activation. Thus, the induction of epidermal differentiation by Fra-2 is controlled by a dual mechanism involving Ezh2-dependent methylation and activation by ERK1/2-dependent phosphorylation.
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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.