A full-genome microarray of the (oxy)photosynthetic cyanobacterium Synechocystis sp. PCC 6803 was used to identify genes that were transcriptionally regulated by growth in iron (Fe)-deficient versus Fe-sufficient media. Transcript accumulation for 3,165 genes in the genome was analyzed using an analysis of variance model that accounted for slide and replicate (random) effects and dye (a fixed) effect in testing for differences in the four time periods. We determined that 85 genes showed statistically significant changes in the level of transcription (P Յ 0.05/3,165 ϭ 0.0000158) across the four time points examined, whereas 781 genes were characterized as interesting (P Յ 0.05 but greater than 0.0000158; 731 of these had a fold change Ͼ1.25ϫ). The genes identified included those known previously to be Fe regulated, such as isiA that encodes a novel chlorophyll-binding protein responsible for the pigment characteristics of low-Fe (LoFe) cells. ATP synthetase and phycobilisome genes were down-regulated in LoFe, and there were interesting changes in the transcription of genes involved in chlorophyll biosynthesis, in photosystem I and II assembly, and in energy metabolism. Hierarchical clustering demonstrated that photosynthesis genes, as a class, were repressed in LoFe and induced upon the re-addition of Fe. Specific regulatory genes were transcriptionally active in LoFe, including two genes that show homology to plant phytochromes (cph1 and cph2). These observations established the existence of a complex network of regulatory interactions and coordination in response to Fe availability.Fe is an essential element that is required for the growth and development of all organisms, including microorganisms (Hantke, 2001) and plants (Thimm et al., 2001;Negishi et al., 2002). Although Fe is abundant in nature, the availability of this element is very limited because of its poor solubility in aerobic environments. In the presence of oxygen at physiological pH, the rapid oxidation of the ferrous form to the ferric form leads to the precipitation of Fe and its essential unavailability. Thus, living organisms have developed various mechanisms to solubilize Fe to improve its bioavailability (Fox and Guerinot, 1998;Ratledge and Dover, 2000). Fe is of great importance for the growth of both pathogenic and nonpathogenic bacteria, and many strains devote a significant portion of their genome to the regulation of and the acquisition of Fe (Earhart, 1996;Paustian et al., 2001).Cyanobacteria are (oxy)photosynthetic organisms in which Fe stress has been studied in some detail (Straus, 1994;Behrenfeld and Kolber, 1999). Fe deficiency results in a variety of physiological and morphological changes in cyanobacteria, the most obvious of which is a significant change in cellular pigmentation. The overall changes include: loss of the light-harvesting phycobilisomes (Guikema and Sherman, 1983), changes in the fluorescence and absorption characteristics Sherman, 1983, 1984;Pakrasi et al., 1985aPakrasi et al., , 1985b, reduction in the numbe...