Characterization of a New Circadian Clock Gene Gm129 Public Deposited
- Last Modified
- March 19, 2019
- Creator
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Annayev, Yunus
- Affiliation: School of Medicine, Department of Biochemistry and Biophysics
- Abstract
- Circadian clock is a 24hr rhythmicity that controls behavioral, metabolic events in most of the organisms. It has been reported that around 10% of all transcripts in mice show circadian expression pattern. The circadian clock is regulated by core clock which in most organisms is controlled by a transcription-translation feedback loop (TTFL). Transcriptional activators constitute positive arm of the TTFL and transcriptional repressors constitute the negative arm of the (TTFL). In a ChIPseq analysis in mice liver we found that core clock genes bind strongly to the promoter of a previously uncharacterized gene called Gene Model 129 (Gm129). Gm129 transcript and the protein show a very high amplitude oscillation in mouse liver. Given these core clock gene like characteristics of Gm129, I analyzed its function in the core clock and found that it interacts with BMAL1 and PER2. Additionally, Gm129 binds to BMAL1/DNA complex both in vitro and in vivo. In the reporter gene assay it inhibits CLOCK/BMAL1 induced transcription suggesting that it functions as a repressor. Gm129 knock-out mice show altered circadian transcription of clock genes and this effect is more dramatic when Gm129 mutation was combined with Cry1 mutation. Overall, I have demonstrated that Gm129 is novel circadian clock repressor. Characterization of Gm129 provides more insight on how the circadian clock machinery functions in mammalian organisms.
- Date of publication
- May 2014
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- Subject
- DOI
- Identifier
- Resource type
- Rights statement
- In Copyright
- Advisor
- Marzluff, William
- Sancar, Aziz
- Crews, Stephen
- Strahl, Brian
- Wang, Greg
- Degree
- Doctor of Philosophy
- Degree granting institution
- University of North Carolina at Chapel Hill Graduate School
- Graduation year
- 2014
- Language
- Publisher
- Place of publication
- Chapel Hill, NC
- Access
- There are no restrictions to this item.
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