Abstract
Signaling pathways often transmit multiple signals through a single shared transcription factor (TF) and encode signal information by differentially regulating TF dynamics. However, signal information will be lost unless it can be reliably decoded by downstream genes. To understand the limits on dynamic information transduction, we apply information theory to quantify how much gene expression information the yeast TF Msn2 can transduce to target genes in the amplitude or frequency of its activation dynamics. We find that although the amount of information transmitted by Msn2 to single target genes is limited, information transduction can be increased by modulating promoter cis-elements or by integrating information from multiple genes. By correcting for extrinsic noise, we estimate an upper bound on information transduction. Overall, we find that information transduction through amplitude and frequency regulation of Msn2 is limited to error-free transduction of signal identity, but not signal intensity information.
Highlights
Cellular signaling pathways often exhibit a bowtie topology (Csete and Doyle, 2004): multiple distinct signal inputs converge on a single master regulator, typically a transcription factor (TF), which controls the expression of partially overlapping sets of downstream target genes
We focus on the response of single genes and ask: can cells reliably transmit both signal identity and intensity information in the amplitude and frequency of TFs to target genes in the presence of biochemical noise? In other words, what are the limits on amplitude- and frequency-mediated information transduction? We investigate this by applying tools from information theory to quantify how much of the information encoded in the amplitude and frequency of a TF can be transmitted through gene promoters to fine-tune the gene expression level
A ‘blackbox’-framework, information theory was originally developed for telecommunication channels, but it can be applied to other ‘channels’ such as gene promoters or cell signaling pathways provided that the signal input can be precisely controlled and the response output distribution precisely measured
Summary
Cellular signaling pathways often exhibit a bowtie topology (Csete and Doyle, 2004): multiple distinct signal inputs converge on a single master regulator, typically a transcription factor (TF), which controls the expression of partially overlapping sets of downstream target genes. Beyond p53 and Msn, amplitude- or frequency encoding of signal identity and intensity information is conserved throughout eukaryotic signaling pathways (see Berridge et al, 2000; Werner et al, 2005; Cai et al, 2008; Warmflash et al, 2012; Albeck et al, 2013; Aoki et al, 2013; Imayoshi et al, 2013; Dalal et al, 2014; Harima et al, 2014) Such encoding of signal identity and intensity information in TF activation dynamics has led to the hypothesis that TF target genes can reliably decode this dynamical information to elicit distinct gene expression programs with
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