Histone H2B monoubiquitination is a critical epigenetic switch for the regulation of autophagy

Nucleic Acids Res. 2017 Feb 17;45(3):1144-1158. doi: 10.1093/nar/gkw1025.

Abstract

Autophagy is an evolutionarily conserved cellular process that primarily participates in lysosome-mediated protein degradation. Although autophagy is a cytoplasmic event, how epigenetic pathways are involved in the regulation of autophagy remains incompletely understood. Here, we found that H2B monoubiquitination (H2Bub1) is down-regulated in cells under starvation conditions and that the decrease in H2Bub1 results in the activation of autophagy. We also identified that the deubiquitinase USP44 is responsible for the starvation-induced decrease in H2Bub1. Furthermore, the changes in H2Bub1 affect the transcription of genes involved in the regulation of autophagy. Therefore, this study reveals a novel epigenetic pathway for the regulation of autophagy through H2Bub1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / genetics*
  • Autophagy-Related Proteins / antagonists & inhibitors
  • Autophagy-Related Proteins / genetics
  • Autophagy-Related Proteins / metabolism
  • Cell Differentiation
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methyltransferase 3A
  • DNA Methyltransferase 3B
  • Down-Regulation
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism
  • Endopeptidases / genetics
  • Endopeptidases / metabolism
  • Epigenesis, Genetic*
  • Gene Knockdown Techniques
  • HEK293 Cells
  • HeLa Cells
  • Histones / chemistry
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Mice
  • Models, Biological
  • RNA, Small Interfering / genetics
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism
  • Ubiquitin Thiolesterase
  • Ubiquitin-Specific Proteases / antagonists & inhibitors
  • Ubiquitin-Specific Proteases / genetics
  • Ubiquitin-Specific Proteases / metabolism
  • Ubiquitination / genetics*

Substances

  • Autophagy-Related Proteins
  • DNMT3A protein, human
  • Histones
  • RNA, Small Interfering
  • Tumor Suppressor Proteins
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • Endopeptidases
  • USP44 protein, human
  • USP44 protein, mouse
  • Ubiquitin Thiolesterase
  • Ubiquitin-Specific Proteases