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The transcriptional output of a cell reflects the sum of cooperative and competing interactions among hundreds of transcriptional regulators that are themselves regulated according to cellular conditions. In this way, disparate signaling cascades intersect at the level of gene expression; perturbation in one area of the cell will necessarily and fundamentally affect other areas as the cell strives to integrate information from multiple pathways. The consequences of such transcriptional cross-talk are highlighted by a newly discovered connection, through a common co-regulator, between stress in the endoplasmic reticulum and control of gluconeogenesis. These findings hint at the possible functions of stress pathways as regulators of basal cellular homeostasis.