NDLI: Gene model 129 (Gm129) encodes a novel transcriptional repressor that modulates circadian gene expression.

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Gene model 129 (Gm129) encodes a novel transcriptional repressor that modulates circadian gene expression.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Adar, Sheera Chiou, Yi-ying Lieb, Jason D. Ye, Rui Annayev, Yunus Sancar, Aziz
Description	Author Affiliation: Annayev Y ( From the Departments of Biochemistry and Biophysics and.)
Abstract	The mammalian circadian clock is a molecular oscillator composed of a feedback loop that involves transcriptional activators CLOCK and BMAL1, and repressors Cryptochrome (CRY) and Period (PER). Here we show that a direct CLOCK·BMAL1 target gene, Gm129, is a novel regulator of the feedback loop. ChIP analysis revealed that the CLOCK·BMAL1·CRY1 complex strongly occupies the promoter region of Gm129. Both mRNA and protein levels of GM129 exhibit high amplitude circadian oscillations in mouse liver, and Gm129 gene encodes a nuclear-localized protein that directly interacts with BMAL1 and represses CLOCK·BMAL1 activity. In vitro and in vivo protein-DNA interaction results demonstrate that, like CRY1, GM129 functions as a repressor by binding to the CLOCK·BMAL1 complex on DNA. Although Gm129(-/-) or Cry1(-/-) Gm129(-/-) mice retain a robust circadian rhythm, the peaks of Nr1d1 and Dbp mRNAs in liver exhibit a significant phase delay compared with control. Our results suggest that, in addition to CRYs and PERs, the GM129 protein contributes to the transcriptional feedback loop by modulating CLOCK·BMAL1 activity as a transcriptional repressor.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	8
Volume Number	289
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2014-02-21
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Circadian Clocks Genetics Gene Expression Regulation Repressor Proteins Metabolism Transcription, Genetic Animals CLOCK Proteins Cell Nucleus Chromatin Immunoprecipitation Cryptochromes DNA Liver Mice Mice, Knockout Models, Biological Multiprotein Complexes NIH 3T3 Cells Nuclear Proteins Protein Binding Protein Transport Deficiency Research Support, N.I.H., Extramural Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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