UTX coordinates steroid hormone-mediated autophagy and cell death
Open accessAbstract
Correct spatial and temporal induction of numerous cell type-specific genes during development requires regulated removal of the repressive histone H3 lysine 27 trimethylation (H3K27me3) modification. Here we show that the H3K27me3 demethylase dUTX is required for hormone-mediated transcriptional regulation of apoptosis and autophagy genes during ecdysone-regulated programmed cell death of Drosophila salivary glands. We demonstrate that dUTX binds to the nuclear hormone receptor complex Ecdysone Receptor/Ultraspiracle, and is recruited to the promoters of key apoptosis and autophagy genes. Salivary gland cell death is delayed in dUTX mutants, with reduced caspase activity and autophagy that coincides with decreased apoptosis and autophagy gene transcripts. We further show that salivary gland degradation requires dUTX catalytic activity. Our findings provide evidence for an unanticipated role for UTX demethylase activity in regulating hormone-dependent cell death and demonstrate how a single transcriptional regulator can modulate a specific complex functional outcome during animal development.
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Developmental degradation of Drosophila salivary glands by autophagy requires Utx, miR-14, Rala, Drpr, and Mcr.
“Moreover, the developmental degradation of Drosophila salivary glands by autophagy requires the activity of: (1) Utx histone demethylase (Utx), which contributes to the transcriptional regulation of apoptosis and autophagy genes [839]; (2) miR-14, which specifically activates autophagy-dependent cell death by modulating multiple IP3-driven signaling pathways upon targeting inositol 1,4,5-triphosph”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [839]
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- Authors
- Denton, D., Aung-Htut, M. T., Lorensuhewa, N., Nicolson, S., Zhu, W., Mills, K., Cakouros, D., Bergmann, A., & Kumar, S.
- Affiliations
- South Australia Pathology (AU)
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Kumar, Sharad
- Venue
- Nature Communications
- Published
- 2013-12-13
- Volume
- 4
- Issue
- 1
- Pages
- 2916-2916
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC3973156
- OpenAlex
- W2002888964
- Cited by
- 58
- References
- 54
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 1 · 2023: 5 · 2022: 3 · 2021: 6 · 2020: 3 · 2019: 5 · 2018: 6 · 2017: 3 · 2016: 5 · 2015: 9 · 2014: 5
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- National Institutes of Health
- Medical Research Council
- National Health and Medical Research Council (1002863, 626923)
- National Institute of General Medical Sciences (R01GM068016)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- ecdysone receptor, ultraspiracle, apoptosis, autophagy, caspase activity, larval-pupal transition, Drosophila, histone modifications, transcriptional regulation
- MeSH terms
- Animals, Autophagy, DNA-Binding Proteins, Drosophila, Ecdysone, Histones, Larva, Methylation, Mutation, Oxidoreductases, N-Demethylating, Promoter Regions, Genetic, Receptors, Steroid, Salivary Glands, Transcription Factors, Cell Death, Apoptosis, Gene Expression Regulation, Developmental, Caspases, Drosophila Proteins
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