For S. elongatus, circadian oscillation Roxadustat patterns have been demonstrated for almost all genes or at least 30% of all genes, depending on the experimental set-up, conditions and data analysis ( Ito et al., 2009, Liu et al., 1995, Nakahira et al., 2004 and Vijayan

et al., 2009). The consensus view of the clock output pathway is that factors such as SasA, RpaA, LabA as well as CikA with its dual role in input and output regulate downstream gene expression, including kaiBC expression ( Gutu and O’Shea, 2013, Iwasaki et al., 2000, Schmitz et al., 2000, Takai et al., 2006 and Taniguchi et al., 2007). In particular, the histidine kinase SasA (Synechococcus adaptive sensor) constitutes a key component of the output pathway. It interacts physically with KaiC, autophosphorylates and transfers the phosphate to its cognate OmpR-type response regulator RpaA (regulator of phycobilisome-associated; Iwasaki et al., 2000 and Takai et al., 2006). Phosphorylated RpaA

activates kaiBC expression through a so far unknown mechanism because its direct binding has not been shown ( Hanaoka et al., 2012). Activation of kaiBC expression via the KaiC-SasA-RpaA pathway is proposed to occur mainly during the day ( Taniguchi et al., 2010). this website LabA (low-amplitude and bright) and CikA, on the other hand, repress RpaA activity and constitute negative regulators of kaiBC expression ( Gutu and O’Shea, 2013, Taniguchi et al., 2007 and Taniguchi et al., 2010). In a complementary scenario, the circadian clock might regulate gene expression globally by controlling compaction of the chromosome and Pregnenolone DNA supercoiling ( Mori and Johnson, 2001, Smith and Williams, 2006, Vijayan et al., 2009 and Woelfle et al., 2007). Detailed knowledge on how the circadian clock works in the marine lineage of Cyanobacteria is missing due to the lack of effective genetic manipulation systems. Nevertheless, several studies have been published generating the basis of our

present knowledge of circadian and diel regulation in marine species. Some of the first examples for daily oscillations have been reported for nitrogen fixation in marine Cyanobacteria. They very likely orchestrate their metabolic activities with a circadian clock and, in doing so have found different strategies to protect their nitrogenase from damage by photosynthetically produced oxygen. For instance, Cyanothece sp. ATCC 51142 and Crocosphaera watsonii WH 8501 segregate nitrogen fixation and photosynthesis in time ( Pennebaker et al., 2010 and Reddy et al., 1993), and Trichodesmium erythraeum IMS 101 lowers oxygen in the vicinity of nitrogenase in anticipation of nitrogen fixation ( Berman-Frank et al., 2001). Gene expression studies demonstrated circadian rhythmicity for individual genes in T. erythraeum IMS101 and C. watsonii WH 8501 ( Chen et al., 1996, Chen et al.