التفاصيل البيبلوغرافية
| العنوان: |
Global histone H2B degradation regulates insulin/IGF signaling‐mediated nutrient stress. |
| المؤلفون: |
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 |
| المصدر: |
EMBO Journal; 10/4/2023, Vol. 42 Issue 19, p1-20, 20p |
| مصطلحات موضوعية: |
UBIQUITINATION, GENETIC testing, INSULIN, GENE expression profiling, GENE expression, TRANSCRIPTION factors, CAENORHABDITIS elegans |
| مستخلص: |
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. Synopsis: The exchange of histones and their variants within nucleosomes plays a crucial role in modulating the epigenome and gene expression. This study shows that ubiquitin‐dependent histone H2B exchange and degradation are crucial in determining C. elegans diapause by regulating the transcriptional activity of DAF‐16/FoxO.Histone H2B undergoes global exchange and degradation during development and starvation in C. elegans.The components of the ubiquitin‐proteasome system (UPS), including ubiquitin/UBQ‐1, E1/UBA‐1, E2/UBC‐20, and E3/HECD‐1, regulate H2B exchange and degradation by ubiquitinating H2B at lysine 31.Disruption of H2B exchange and degradation enhances the binding of DAF‐16/FoxO to chromatin, resulting in aberrant activation or suppression of target genes, and ultimately leading to larval death.Ubiquitin‐dependent histone H2B exchange and degradation are conserved in mammalian cells. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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