A functional genomics strategy reveals Rora as a component of the mammalian circadian clock

Trey K Sato; Satchidananda Panda; Loren J Miraglia; Teresa M Reyes; Radu D Rudic; Peter McNamara; Kinnery A Naik; Garret A FitzGerald; Steve A Kay; John B Hogenesch

doi:10.1016/j.neuron.2004.07.018

A functional genomics strategy reveals Rora as a component of the mammalian circadian clock

Neuron. 2004 Aug 19;43(4):527-37. doi: 10.1016/j.neuron.2004.07.018.

Authors

Trey K Sato¹, Satchidananda Panda, Loren J Miraglia, Teresa M Reyes, Radu D Rudic, Peter McNamara, Kinnery A Naik, Garret A FitzGerald, Steve A Kay, John B Hogenesch

Affiliation

¹ Genomics Institute of the Novartis Research Foundation, 10675 John J. Hopkins Drive, San Diego, California 92121, USA.

PMID: 15312651
DOI: 10.1016/j.neuron.2004.07.018

Abstract

The mammalian circadian clock plays an integral role in timing rhythmic physiology and behavior, such as locomotor activity, with anticipated daily environmental changes. The master oscillator resides within the suprachiasmatic nucleus (SCN), which can maintain circadian rhythms in the absence of synchronizing light input. Here, we describe a genomics-based approach to identify circadian activators of Bmal1, itself a key transcriptional activator that is necessary for core oscillator function. Using cell-based functional assays, as well as behavioral and molecular analyses, we identified Rora as an activator of Bmal1 transcription within the SCN. Rora is required for normal Bmal1 expression and consolidation of daily locomotor activity and is regulated by the core clock in the SCN. These results suggest that opposing activities of the orphan nuclear receptors Rora and Rev-erb alpha, which represses Bmal1 expression, are important in the maintenance of circadian clock function.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

ARNTL Transcription Factors
Animals
Basic Helix-Loop-Helix Transcription Factors
Biological Clocks / genetics*
Circadian Rhythm / genetics*
Genomics / methods*
HeLa Cells
Humans
Mice
Mice, Inbred C57BL
Mice, Neurologic Mutants
Nuclear Receptor Subfamily 1, Group F, Member 1
Promoter Regions, Genetic
RNA, Messenger / biosynthesis
RNA, Messenger / genetics
Receptors, Cytoplasmic and Nuclear
Receptors, Retinoic Acid / biosynthesis
Receptors, Retinoic Acid / genetics*
Response Elements / genetics
Trans-Activators
Transcription Factors / genetics
Transcription Factors / metabolism

Substances

ARNTL Transcription Factors
BMAL1 protein, human
Bmal1 protein, mouse
Basic Helix-Loop-Helix Transcription Factors
Nuclear Receptor Subfamily 1, Group F, Member 1
RNA, Messenger
RORA protein, human
Receptors, Cytoplasmic and Nuclear
Receptors, Retinoic Acid
Rora protein, mouse
Trans-Activators
Transcription Factors