Characterization of a New Circadian Clock Gene Gm129 Public Deposited

Analytics

Downloadable Content

Download PDF
Last Modified
  • March 19, 2019
Creator
  • 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
Keyword
Subject
Identifier
Resource type
Rights statement
  • In Copyright
Advisor
  • Crews, Stephen
  • Sancar, Aziz
  • Marzluff, William
  • 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.
Parents:

This work has no parents.

Items

Thumbnail Title Date Uploaded Visibility Actions
Qz20ss78g?file=thumbnail Annayev_unc_0153D_14646.pdf 2019-04-09 Public