Following the Occam's razor principle (principle of parsimony), M-clock components of unknown molecular origin were excluded from Maltsev Lakatta pacemaker cell model and thirteen different model types of only 4 or 5 components were derived and explored by a parametric sensitivity analysis.
Third, this assay reveals clear circadian phenotypes caused by the knockdown of several clock components, some of which (Bmal1, Cry2, Per1) are similar to those observed in genetic-null murine models.
Interestingly, none of the other clock components and modifiers of the components, including FRH (FRQ-Interacting RNA Helicase), a binding partner of FRQ necessary for negative feedback (Guo et al. 2010), and several kinases (CK1, CK2, PKA, and CAMK-1) and phosphatases (PP1, PP2A, and PP4) that modify the activities of the clock components, met our stringent criteria for light regulation.
In both studies, the loss of Lhx1 in the SCN did not affect the overall expression level of any of the clock components, while the expression of several genes implicated in cellular synchrony including Vip and Avpr1a were downregulated.
These examples illustrating the multiple routes for potential post-translational regulation of clock components emphasize the complexity of the circadian machinery that can provide control points for fine-tuning the pacemaker.
Orthologs of circadian clock components in plants outside of Arabidopsis have been best characterized in rice [ 20] and Lemna [ 21].
Alternatively, expression of certain clock components or key elements of temperature sensing signal transduction pathways may not yet have matured prior to the second day of development.
Thus most characterized clock components repress expression of other clock components.
Likewise, the use of genetic knockout mutants of circadian clock genes can reduce disruptions due to circadian input; However, since stress response genes may be regulated by clock components, the results of such a study are also difficult to interpret [ 7, 19, 20].
In addition, PRR7, PRR5, and TOC1 repress the gene expression of many clock components simultaneously around the end of the day and the beginning of the night.
