Histone H2B monoubiquitination is a critical epigenetic switch for the regulation of autophagy.
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.
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Advanced Institute of Translational Medicine, Tongji University, Shanghai, PR China.|School of Forensic Sciences, Xi'an Jiao Tong University Health Science Center, Xi'an, Shaanxi, PR China.|Department of Science and Education, People's Hospital of Zunhua, Tangshan, Hebei, PR China
Su
S
Chen
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Advanced Institute of Translational Medicine, Tongji University, Shanghai, PR China.
Yuanya
Y
Jing
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Advanced Institute of Translational Medicine, Tongji University, Shanghai, PR China.
Xuan
X
Kang
Research Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiao Tong University, Shaanxi 710061, PR China.
Lu
L
Yang
School of Medicine, Tsinghua University, Beijing 100084, PR China.
Da-Liang
DL
Wang
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Advanced Institute of Translational Medicine, Tongji University, Shanghai, PR China.
Wei
W
Zhang
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Advanced Institute of Translational Medicine, Tongji University, Shanghai, PR China.
Lei
L
Zhang
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Advanced Institute of Translational Medicine, Tongji University, Shanghai, PR China.
Ping
P
Chen
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Advanced Institute of Translational Medicine, Tongji University, Shanghai, PR China.
Jian-Feng
JF
Chang
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Advanced Institute of Translational Medicine, Tongji University, Shanghai, PR China.
Xiao-Mei
XM
Yang
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Advanced Institute of Translational Medicine, Tongji University, Shanghai, PR China.
Fang-Lin
FL
Sun
D000818:Animals; D001343:Autophagy / Q000235:genetics*; D000071183:Autophagy-Related Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D000090205:DNA Methyltransferase 3A; D015536:Down-Regulation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D034741:RNA, Small Interfering / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination / Q000235:genetics*; D000097584:DNA Methyltransferase 3B
D000071183:Autophagy-Related Proteins; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D010450:Endopeptidases; D006657:Histones; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C579216:USP44 protein, human; C577772:USP44 protein, mouse