UTX coordinates steroid hormone-mediated autophagy and cell death

Donna Denton, May T. Aung-Htut, Nirmal Lorensuhewa, Shannon Nicolson, Wenying Zhu, Kathryn Mills, Dimitrios Cakouros, Andreas Bergmann and Sharad Kumar ()
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Donna Denton: Centre for Cancer Biology, SA Pathology
May T. Aung-Htut: Centre for Cancer Biology, SA Pathology
Nirmal Lorensuhewa: Centre for Cancer Biology, SA Pathology
Shannon Nicolson: Centre for Cancer Biology, SA Pathology
Wenying Zhu: Centre for Cancer Biology, SA Pathology
Kathryn Mills: Centre for Cancer Biology, SA Pathology
Dimitrios Cakouros: Centre for Cancer Biology, SA Pathology
Andreas Bergmann: University of Massachusetts Medical School
Sharad Kumar: Centre for Cancer Biology, SA Pathology

Nature Communications, 2013, vol. 4, issue 1, 1-11

Abstract: 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.

Date: 2013
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DOI: 10.1038/ncomms3916

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