title: UTX coordinates steroid hormone-mediated autophagy and cell death.
abstract: 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.
authors: 1] Centre for Cancer Biology, SA Pathology, Frome Road, Adelaide, South Australia 5000, Australia [2] Division of Health Sciences, University of South Australia, Adelaide, South Australia 5001, Australia.
authors: Donna
authors: D
authors: Denton
authors: Centre for Cancer Biology, SA Pathology, Frome Road, Adelaide, South Australia 5000, Australia.
authors: May T
authors: MT
authors: Aung-Htut
authors: Centre for Cancer Biology, SA Pathology, Frome Road, Adelaide, South Australia 5000, Australia.
authors: Nirmal
authors: N
authors: Lorensuhewa
authors: Centre for Cancer Biology, SA Pathology, Frome Road, Adelaide, South Australia 5000, Australia.
authors: Shannon
authors: S
authors: Nicolson
authors: Centre for Cancer Biology, SA Pathology, Frome Road, Adelaide, South Australia 5000, Australia.
authors: Wenying
authors: W
authors: Zhu
authors: Centre for Cancer Biology, SA Pathology, Frome Road, Adelaide, South Australia 5000, Australia.
authors: Kathryn
authors: K
authors: Mills
authors: Centre for Cancer Biology, SA Pathology, Frome Road, Adelaide, South Australia 5000, Australia.
authors: Dimitrios
authors: D
authors: Cakouros
authors: Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors: Andreas
authors: A
authors: Bergmann
authors: 1] Centre for Cancer Biology, SA Pathology, Frome Road, Adelaide, South Australia 5000, Australia [2] Division of Health Sciences, University of South Australia, Adelaide, South Australia 5001, Australia [3] Department of Medicine, The University of Adelaide, Adelaide, South Australia 5005, Australia.
authors: Sharad
authors: S
authors: Kumar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001343:Autophagy / Q000235:genetics*; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000166:cytology / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004440:Ecdysone / Q000378:metabolism* / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000235:genetics / Q000378:metabolism; D007814:Larva; D008745:Methylation; D009154:Mutation; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism; D012469:Salivary Glands / Q000166:cytology* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C095837:Eip93F protein, Drosophila; D006657:Histones; D011987:Receptors, Steroid; D014157:Transcription Factors; C066030:USP protein, Drosophila; C055469:ecdysone receptor; D004440:Ecdysone; D010089:Oxidoreductases, N-Demethylating; C527283:UTX protein, Drosophila; D020169:Caspases