Context-specific regulation of lysosomal lipolysis through network-level diverting of transcription factor interactions

Abstract

Significance Genes often encode for proteins with specialized functions (e.g., lipase). However, the function of the protein, and hence the gene, may be critical for survival in diverse contexts (e.g., fasting and oxidative stress). Hence, how are common survival genes activated in multiple contexts? Based on genetics and mathematical modeling, we describe two modes of transcriptional activation: 1) convergent—a single transcriptional regulator activates the survival gene in multiple contexts—and 2) contextual—the activity/interaction of members of a network of transcriptional regulators is fine-tuned to activate the survival gene through molecular paths that are specific to a context. The results underscore the limitations of across-context molecular inferences and suggest an economic tactic to biological resilience.