ArticleProceedings of the National Academy of Sciences of the United States of America2018
Steroidogenic differentiation and PKA signaling are programmed by histone methyltransferase EZH2 in the adrenal cortex.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 56 citations in OpenAlex.
- Human and mouse adrenal glands are characterized by species-specific steroidogenic states and tissue turnover.Nature genetics · 2026Article
- The Effects of ACTH and Dexamethasone on the Transcriptomic Profile of the Rat Adrenal Gland: An In Vivo Study.Current issues in molecular biology · 2026Article
- The transcription factor HHEX maintains glucocorticoid levels and protects adrenals from androgen-induced lipid depletion.Nature communications · 2026Article
- Adrenocortical stem cells in health and disease.Nature reviews. Endocrinology · 2025Review
- Dlk1 is a novel adrenocortical stem/progenitor cell marker that predicts malignancy in adrenocortical carcinoma.Cancer communications (London, England) · 2025Article
- Hippo Signaling Is Essential for the Maintenance of Zona Glomerulosa Cell Fate in the Murine Adrenal Cortex.Endocrinology · 2025Article
- Article
- Wild-type bone marrow cells repopulate tissue resident macrophages and reverse the impacts of homozygous CSF1R mutation.PLoS genetics · 2025Article
- Exploration of the potential of genomic editing in the treatment of congenital adrenal hyperplasia.Frontiers in endocrinology · 2025Review
- Dlk1 is a novel adrenocortical stem/progenitor cell marker that predicts malignancy in adrenocortical carcinoma.bioRxiv : the preprint server for biology · 2024Article
- Current insight into the transient X-zone in the adrenal gland cortex.Vitamins and hormones · 2024Review
- Age-related Changes in the Adrenal Cortex: Insights and Implications.Journal of the Endocrine Society · 2023Review
- β-Catenin-Driven Differentiation Is a Tissue-Specific Epigenetic Vulnerability in Adrenal Cancer.Cancer research · 2023Article
- Loss of SUMO-specific protease 2 causes isolated glucocorticoid deficiency by blocking adrenal cortex zonal transdifferentiation in mice.Nature communications · 2022Article
- Update on Biology and Genomics of Adrenocortical Carcinomas: Rationale for Emerging Therapies.Endocrine reviews · 2022Article
- Transgenic Mouse Models to Study the Development and Maintenance of the Adrenal Cortex.International journal of molecular sciences · 2022Review
- Effect of Inactivation ofJournal of the Endocrine Society · 2022Article
- Regulatory roles of alternative splicing at Ezh2 gene in mouse oocytes.Reproductive biology and endocrinology : RB&E · 2022Article
- Embryonic osteocalcin signaling determines lifelong adrenal steroidogenesis and homeostasis in the mouse.The Journal of clinical investigation · 2022Article
- [Adrenal glands stem cells: general signaling pathways].Problemy endokrinologii · 2021Article
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Authors and funding
20 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adrenal cortex steroids are essential for body homeostasis, and adrenal insufficiency is a life-threatening condition. Adrenal endocrine activity is maintained through recruitment of subcapsular progenitor cells that follow a unidirectional differentiation path from zona glomerulosa to zona fasciculata (zF). Here, we show that this unidirectionality is ensured by the histone methyltransferase EZH2. Indeed, we demonstrate that EZH2 maintains adrenal steroidogenic cell differentiation by preventing expression of GATA4 and WT1 that cause abnormal dedifferentiation to a progenitor-like state in Ezh2 KO adrenals. EZH2 further ensures normal cortical differentiation by programming cells for optimal response to adrenocorticotrophic hormone (ACTH)/PKA signaling. This is achieved by repression of phosphodiesterases PDE1B, 3A, and 7A and of PRKAR1B. Consequently, EZH2 ablation results in blunted zF differentiation and primary glucocorticoid insufficiency. These data demonstrate an all-encompassing role for EZH2 in programming steroidogenic cells for optimal response to differentiation signals and in maintaining their differentiated state.
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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.