The Transcription Factor Runx2 Is under Circadian Control in the Suprachiasmatic Nucleus and Functions in the Control of Rhythmic Behavior

Runx2, a member of the family of runt-related transcription factors, is rhythmically expressed in bone and may be involved in circadian rhythms in bone homeostasis and osteogenesis. Runx2 is also expressed in the brain, but its function is unknown. We tested the hypothesis that in the brain, Runx2 m...

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Vydáno v:	PloS one Ročník 8; číslo 1; s. e54317
Hlavní autoři:	Reale, Meghan E., Webb, Ian C., Wang, Xu, Baltazar, Ricardo M., Coolen, Lique M., Lehman, Michael N.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 25.01.2013 Public Library of Science (PLoS)
Témata:	Analysis Animal behavior Animals ARNTL Transcription Factors - deficiency ARNTL Transcription Factors - genetics Biocompatibility Biological clocks Biology Bioluminescence Biomedical materials BMAL1 protein Bone turnover Brain Cbfa-1 protein Circadian Clocks - genetics Circadian rhythm Circadian Rhythm - genetics Circadian rhythms Clock gene CLOCK protein Core Binding Factor Alpha 1 Subunit - deficiency Core Binding Factor Alpha 1 Subunit - genetics Diurnal DNA binding proteins Gene expression Gene Expression Regulation Genes Homeostasis Male Mice Mice, Transgenic Motor Activity - physiology Mutation Nuclei Olfactory bulb Olfactory Bulb - physiology Osteogenesis Paraventricular Hypothalamic Nucleus - physiology Paraventricular nucleus Period 1 protein Period 2 protein Period Circadian Proteins - genetics Period Circadian Proteins - metabolism Rhythms RNA RNA, Messenger - genetics RNA, Messenger - metabolism Rodents Signal Transduction Suprachiasmatic nucleus Suprachiasmatic Nucleus - physiology Transcription factors Transcription, Genetic Wheel running Ontario Canada Canada Mississippi United States > US
ISSN:	1932-6203, 1932-6203
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Shrnutí:	Runx2, a member of the family of runt-related transcription factors, is rhythmically expressed in bone and may be involved in circadian rhythms in bone homeostasis and osteogenesis. Runx2 is also expressed in the brain, but its function is unknown. We tested the hypothesis that in the brain, Runx2 may interact with clock-controlled genes to regulate circadian rhythms in behavior. First, we demonstrated diurnal and circadian rhythms in the expression of Runx2 in the mouse brain. Expression of Runx2 mRNA and protein mirrored that of the core clock genes, Period1 and Period2, in the suprachiasmatic nucleus (SCN), the paraventricular nucleus and the olfactory bulb. The rhythm of Runx2 expression was eliminated in the SCN of Bmal1(-/-) mice. Moreover, by crossbreeding mPer2(Luc) mice with Runx2(+/-) mice and recording bioluminescence rhythms, a significant lengthening of the period of rhythms was detected in cultured SCN of Runx2(-/-) animals compared to either Runx2(+/-) or Runx2(+/+) mice. Behavioral analyses of Runx2 mutant mice revealed that Runx2(+/-) animals displayed a significantly lengthened free-running period of running wheel activity compared to Runx2(+/+) littermates. Taken together, these findings provide evidence for clock gene-mediated rhythmic expression of Runx2, and its functional role in regulating circadian period at the level of the SCN and behavior.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Conceived and designed the experiments: MER LMC MNL. Performed the experiments: MER ICW XW RMB LMC. Analyzed the data: MER LMC MNL. Wrote the paper: MER ICW LMC MNL. Competing Interests: The authors have declared that no competing interests exist.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0054317