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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autophagy / genetics*
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Autophagy-Related Proteins / antagonists & inhibitors
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Autophagy-Related Proteins / genetics
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Autophagy-Related Proteins / metabolism
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Cell Differentiation
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DNA (Cytosine-5-)-Methyltransferases / metabolism
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DNA Methyltransferase 3A
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DNA Methyltransferase 3B
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Down-Regulation
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Embryonic Stem Cells / cytology
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Embryonic Stem Cells / metabolism
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Endopeptidases / genetics
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Endopeptidases / metabolism
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Epigenesis, Genetic*
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Gene Knockdown Techniques
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HEK293 Cells
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HeLa Cells
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Histones / chemistry
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Histones / genetics
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Histones / metabolism*
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Humans
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Mice
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Models, Biological
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RNA, Small Interfering / genetics
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism
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Ubiquitin Thiolesterase
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Ubiquitin-Specific Proteases / antagonists & inhibitors
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Ubiquitin-Specific Proteases / genetics
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Ubiquitin-Specific Proteases / metabolism
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Ubiquitination / genetics*
Substances
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Autophagy-Related Proteins
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DNMT3A protein, human
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Histones
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RNA, Small Interfering
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Tumor Suppressor Proteins
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DNA (Cytosine-5-)-Methyltransferases
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DNA Methyltransferase 3A
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Endopeptidases
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USP44 protein, human
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USP44 protein, mouse
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Ubiquitin Thiolesterase
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Ubiquitin-Specific Proteases