UTX coordinates steroid hormone-mediated autophagy and cell death

Nat Commun. 2013;4:2916. doi: 10.1038/ncomms3916.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Autophagy / genetics*
  • Caspases / genetics
  • Caspases / metabolism
  • Cell Death / drug effects
  • Cell Death / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Drosophila / cytology
  • Drosophila / genetics
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Ecdysone / metabolism*
  • Ecdysone / pharmacology
  • Gene Expression Regulation, Developmental
  • Histones / genetics
  • Histones / metabolism
  • Larva
  • Methylation
  • Mutation
  • Oxidoreductases, N-Demethylating / genetics
  • Oxidoreductases, N-Demethylating / metabolism*
  • Promoter Regions, Genetic
  • Receptors, Steroid / genetics
  • Receptors, Steroid / metabolism
  • Salivary Glands / cytology*
  • Salivary Glands / physiology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Eip93F protein, Drosophila
  • Histones
  • Receptors, Steroid
  • Transcription Factors
  • USP protein, Drosophila
  • ecdysone receptor
  • Ecdysone
  • Oxidoreductases, N-Demethylating
  • UTX protein, Drosophila
  • Caspases