In summary, we have identified a novel function of Rev-erbβ, being a transcriptional activator in the presence and absence of hemin. Studies have shown that apart from the C-terminal Ligand Binding Domain (LBD), nuclear receptors can also modulate gene AP 26113 using their N-terminus Activation Function-1 (AF-1) domain [38] and [39]. Interestingly, the Rev-erbβ AF-1 domain has been shown to be functional [40]. Raghuram and colleagues have recently shown that heme associates with the LBD of Rev-erbα and β [10] and [11] and demonstrated that the LBD of these NRs form several different confirmations structures in response to heme, NO or CO and redox state. Interestingly, our data shows that Rev-erbβ activates the Srebp-1c promoter in skeletal muscle cells. These observations raise the interesting question whether Rev-erb ligands function in tissue specific manner, and strongly indicate that Rev-erbβ can directly induce and silence gene expression.
CLA; Gene expression; LXR; Macrophages; Nuclear receptor