Emergence of temporal noise hierarchy in co-regulated genes of multi-output feed-forward loop

Abstract Natural variations in gene expression, called noise, are fundamental to biological systems. The expression noise can be beneficial or detrimental to cellular functions. While the impact of noise on individual genes is well-established, our understanding of how noise behaves when multiple genes are co-expressed by shared regulatory elements within transcription networks remains elusive. This lack of understanding extends to how the architecture and regulatory features of these networks influence noise. To address this gap, we study the multi-output feed-forward loop motif. The motif is prevalent in bacteria and yeast and influences co-expression of multiple genes by shared transcription factors (TFs). Focusing on a two-output variant of the motif, the present study explores the interplay between its architecture, co-expression (symmetric and asymmetric) patterns of the two genes, and the associated noise dynamics. We employ a stochastic modeling approach to investigate how the binding affinities of the TFs influence symmetric and asymmetric expression patterns and the resulting noise dynamics in the co-expressed genes. This knowledge could guide the development of strategies for manipulating gene expression patterns through targeted modulation of TF binding affinities.