UTX coordinates steroid hormone-mediated autophagy and cell death

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dc.contributor.authorDenton, D.
dc.contributor.authorAung Htut, M.
dc.contributor.authorLorensuhewa, N.
dc.contributor.authorNicholson, S.
dc.contributor.authorZhu, W.
dc.contributor.authorMills, K.
dc.contributor.authorCakouros, D.
dc.contributor.authorBergmann, A.
dc.contributor.authorKumar, S.
dc.date.issued2013
dc.description.abstractCorrect 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.
dc.description.statementofresponsibilityDonna Denton, May T. Aung-Htut, Nirmal Lorensuhewa, Shannon Nicolson, Wenying Zhu, Kathryn Mills, Dimitrios Cakouros, Andreas Bergmann & Sharad Kumar
dc.identifier.citationNature Communications, 2013; 4(1):1-11
dc.identifier.doi10.1038/ncomms3916
dc.identifier.issn2041-1723
dc.identifier.issn2041-1723
dc.identifier.orcidCakouros, D. [0000-0001-6136-0761]
dc.identifier.orcidKumar, S. [0000-0001-7126-9814]
dc.identifier.urihttp://hdl.handle.net/2440/82601
dc.language.isoen
dc.publisherNature Publishing Group
dc.rights© 2013 Macmillan Publishers Limited. All Rights Reserved.
dc.source.urihttps://doi.org/10.1038/ncomms3916
dc.subjectBiological sciences
dc.subjectCell biology
dc.titleUTX coordinates steroid hormone-mediated autophagy and cell death
dc.typeJournal article
pubs.publication-statusPublished

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