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Nipped‐A regulates the Drosophila circadian clock via histone deubiquitination
Author(s) -
Bu Bei,
Chen Lixia,
Zheng Liubin,
He Weiwei,
Zhang Luoying
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2018101259
Subject(s) - china , christian ministry , chinese academy of sciences , library science , political science , engineering , computer science , law
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.