Nipped-A regulates the Drosophila circadian clock via histone deubiquitination.,The EMBO Journal

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Nipped-A regulates the Drosophila circadian clock via histone deubiquitination.
The EMBO Journal ( IF 9.4 ) Pub Date : 2019-09-19 , DOI: 10.15252/embj.2018101259
Bei Bu _{1,

2} , Lixia Chen ₁ , Liubin Zheng ₁ , Weiwei He ₁ , Luoying Zhang _{1,

3}

Affiliation

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 1ε (Pdp1ε). Furthermore, we found that NIPPED-A promotes the transcription of tim and Pdp1ε 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.

中文翻译：

Nipped-A 通过组蛋白去泛素化调节果蝇生物钟。

精神疾病通常伴随着昼夜节律紊乱，但其分子基础仍不清楚。为了解决这个问题，我们筛选了之前报道的与精神疾病相关的基因，发现与精神分裂症相关的基因TRRAP参与昼夜节律调节。敲低 Nipped-A（人类 TRRAP 的果蝇同源物）会导致果蝇的运动节律周期延长。分子分析表明，NIPPED-A 通过增加核心时钟基因 timeless (tim) 和 Par 结构域蛋白 1ε (Pdp1ε) 的 mRNA 和蛋白质水平来设定时钟的节奏。此外，我们发现 NIPPED-A 可能通过转录共激活因子 Spt-Ada-Gcn5 乙酰转移酶复合物的去泛素化模块促进组蛋白 H2B 去泛素化来促进 tim 和 Pdp1ε 的转录。总而言之，这些发现揭示了 NIPPED-A 在时钟表观遗传调控中的新作用。

更新日期：2020-01-02

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