Circadian Transcription Depends on Limiting Amounts of the Transcription Co-activator nejire/CBP

Hsiu-Cheng Hung,Christian Maurer,Steve A Kay,Frank Weber

doi:10.1074/jbc.m702319200

Hsiu-Cheng Hung, Christian Maurer + Show 2 more

Open Access

https://doi.org/10.1074/jbc.m702319200

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Abstract

The circadian clock orchestrates physiological and behavioral activities, including metabolism, neuronal activity, and cell proliferation in synchrony with the environmental cycle of day and night. Here we show that the Drosophila ortholog of the CBP/p300 family of transcription co-activators, nejire (nej), is an intrinsic component of the circadian clock that performs regulatory functions for circadian controlled transcription. Screening of overexpression mutants revealed that gain of nej function was associated with a loss of behavioral and molecular rhythms. Overexpression of NEJ suppresses the long period phenotype of a mutation in the clock gene period (per). NEJ physically interacts through two binding sites with CLOCK and the CLOCK. CYCLE (CLK.CYC) complex. Induction of CLK.CYC-dependent transcripts upon induction of nej expression from a heat-shock promoter showed that NEJ is limiting. Reduced CLK.CYC-mediated transcription in a nej hypomorphic mutant indicates an essential function of NEJ/CBP for CLK.CYC activity and a regulation of circadian transcription by availability of the co-activator. Competition for recruitment of NEJ/CBP provides a potential mechanism for cross-talk between circadian transcription and other CBP-dependent physiological processes.

Highlights

The circadian clock controls genome wide transcription of many key regulatory components in a diverse selection of vital pathways [1,2,3] that allow a coordination of physiological and behavioral activities and their synchronization with the environmental cycles of day and night
Previous studies showed that recruitment of the CREB-binding protein (CBP) from a limiting cellular pool mediates cross-talk between the transcription factors E2F, JAK/STAT, AP1, and nuclear hormone receptors (14 –16) that control e.g. entry into the cell cycle and the immune response
We show that CLK1⁄7CYC-mediated transcription is dependent on CBP, and importantly circadian transcription responds to changes in limiting levels of the co-activator

Summary

Introduction

The circadian clock controls genome wide transcription of many key regulatory components in a diverse selection of vital pathways [1,2,3] that allow a coordination of physiological and behavioral activities and their synchronization with the environmental cycles of day and night. Overexpression of nej by tim-GAL4 in EP(X)1179 resulted in an increase of behavioral arrhythmicity, without significant effects on general activity levels (Table 1).

Results

Conclusion