Co-existing feedback loops generate tissue-specific circadian rhythms.

ABSTRACT: Gene regulatory feedback loops generate autonomous circadian rhythms in mammalian tissues. The well-studied core clock network contains many negative and positive regulations. Multiple feedback loops have been discussed as primary rhythm generators but the design principles of the core clock and differences between tissues are still under debate. Here we use global optimization techniques to fit mathematical models to circadian gene expression profiles for different mammalian tissues. It turns out that for every investigated tissue multiple model parameter sets reproduce the experimental data. We extract for all model versions the most essential feedback loops and find auto-inhibitions of period and cryptochrome genes, Bmal1-Rev-erb-α loops, and repressilator motifs as possible rhyt

SUBMITTER: Pett JP 

PROVIDER: S-EPMC6238625 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature