Systematic Identification of Rhythmic Genes Reveals camk1gb as a New Element in the Circadian Clockwork

Adi Tovin,Yoav Gothilf,Nicholas S Foulkes,Steven L Coon,Gideon Rechavi,Philipp Mracek,Eli Eisenberg,David C Klein,Gad Vatine,Shahar Alon,Jasmine Jacob-Hirsch,Zohar Ben-Moshe,Reiko Toyama

doi:10.1371/journal.pgen.1003116

Abstract

A wide variety of biochemical, physiological, and molecular processes are known to have daily rhythms driven by an endogenous circadian clock. While extensive research has greatly improved our understanding of the molecular mechanisms that constitute the circadian clock, the links between this clock and dependent processes have remained elusive. To address this gap in our knowledge, we have used RNA sequencing (RNA–seq) and DNA microarrays to systematically identify clock-controlled genes in the zebrafish pineal gland. In addition to a comprehensive view of the expression pattern of known clock components within this master clock tissue, this approach has revealed novel potential elements of the circadian timing system. We have implicated one rhythmically expressed gene, camk1gb, in connecting the clock with downstream physiology of the pineal gland. Remarkably, knockdown of camk1gb disrupts locomotor activity in the whole larva, even though it is predominantly expressed within the pineal gland. Therefore, it appears that camk1gb plays a role in linking the pineal master clock with the periphery.

Highlights

All organisms demonstrate a wide variety of physiological, biochemical and behavioral daily rhythms that are driven by intrinsic oscillators, known as circadian clocks
We take advantage of another attraction of the zebrafish, the fact that its pineal gland is the site of a central clock which directly receives light input and autonomously generates circadian rhythms that affect the physiology of the whole organism
We show that the systematic design and analysis of genome-wide experiments based on the zebrafish pineal gland can lead to the discovery of new clock elements

Summary

Introduction

All organisms demonstrate a wide variety of physiological, biochemical and behavioral daily rhythms that are driven by intrinsic oscillators, known as circadian clocks. These oscillators work in harmony with the 24 hours periodic changes in environmental conditions. Several output genes contribute to the accuracy and stability of the oscillator These encode transcriptional regulators, which constitute accessory loops that feedback to the core loops, or post-translational modifiers of core clock proteins. This system regulates diverse biochemical pathways which are thought to lead to the wide variety of physiological and behavioral daily rhythms [2].

Objectives

Methods

Results

Discussion

Conclusion