The small regulatory protein Crl controls the expression of curli. We have recently shown that Crl interacts directly with one of the most global regulators of Escherichia coli, the stress related sigma factor RpoS, suggesting a more global role for Crl. We show here by a proteomic analysis that the expression of at least nine cellular proteins is considerably modified when Crl is overexpressed. We assess the part of transcriptional and posttranscriptional regulation for five of these genes. The results show that Crl regulates the expression of another global regulator: the central regulator of iron homeostasis, Fur. A molecular analysis reveals that Crl and Fur affect their own and each other's expression. We provide physical evidence for the binding of Fur to the crl and fur promoter regions. Crl modulates the affinity of Fur at the fur-promoter, but not at the crl-promoter. The triade RpoS-Crl-Fur may thus represent the centerpiece of a global regulatory system of response to different stresses.