Details

Autor(en) / Beteiligte

• Zhu, Zhiwen
• Li, Dongdong
• Jia, Zeran
• Zhang, Wenhao
• Chen, Yuling
• Zhao, Ruixue
• Zhang, Yan-Ping
• Zhang, Wen-Hong
• Deng, Haiteng
• Li, Yinqing
• Li, Wei
• Guang, Shouhong
• Ou, Guangshuo

Titel

Global histone H2B degradation regulates insulin/IGF signaling-mediated nutrient stress

Ist Teil von

• The EMBO journal, 2023-10, Vol.42 (19), p.e113328-e113328

Ort / Verlag

England: Blackwell Publishing Ltd

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• Eukaryotic organisms adapt to environmental fluctuations by altering their epigenomic landscapes and transcriptional programs. Nucleosomal histones carry vital epigenetic information and regulate gene expression, yet the mechanisms underlying chromatin-bound histone exchange remain elusive. Here, we found that histone H2Bs are globally degraded in Caenorhabditis elegans during starvation. Our genetic screens identified mutations in ubiquitin and ubiquitin-related enzymes that block H2B degradation in starved animals, identifying lysine 31 as the crucial residue for chromatin-bound H2B ubiquitination and elimination. Retention of aberrant nucleosomal H2B increased the association of the FOXO transcription factor DAF-16 with chromatin, generating an ectopic gene expression profile detrimental to animal viability when insulin/IGF signaling was reduced in well-fed animals. Furthermore, we show that the ubiquitin-proteasome system regulates chromosomal histone turnover in human cells. During larval development, C. elegans epidermal cells undergo H2B turnover after fusing with the epithelial syncytium. Thus, histone degradation may be a widespread mechanism governing dynamic changes of the epigenome.