期刊
EMBO JOURNAL
卷 39, 期 1, 页码 -出版社
WILEY
DOI: 10.15252/embj.2018101259
关键词
circadian clock; Drosophila; histone deubiquitination; NIPPED-A
资金
- Natural Science Foundation of China [31471125, 31671215]
- 1000 Talents Program
Psychiatric diseases are often accompanied by circadian disruptions, but the molecular underpinnings remain largely unclear. To address this, we screened genes that have been previously reported to be associated with psychiatric diseases and found that TRRAP, a gene associated with schizophrenia, is involved in circadian rhythm regulation. Knocking down Nipped-A, the Drosophila homolog of human TRRAP, leads to lengthened period of locomotor rhythms in flies. Molecular analysis demonstrates that NIPPED-A sets the pace of the clock by increasing the mRNA and protein levels of core clock genes timeless (tim) and Par domain protein 1 epsilon (Pdp1 epsilon). Furthermore, we found that NIPPED-A promotes the transcription of tim and Pdp1 epsilon possibly by facilitating deubiquitination of histone H2B via the deubiquitination module of the transcription co-activator Spt-Ada-Gcn5 acetyltransferase complex. Taken together, these findings reveal a novel role for NIPPED-A in epigenetic regulation of the clock.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据