Gene regulation gravitates toward either addition or multiplication when combining the effects of two signals.

Autor:	Sanford EM; Genomics and Computational Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States., Emert BL; Genomics and Computational Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States., Coté A; Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, United States.; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States., Raj A; Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, United States.; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2020 Dec 07; Vol. 9. Date of Electronic Publication: 2020 Dec 07.
DOI:	10.7554/eLife.59388
Abstrakt:	Two different cell signals often affect transcription of the same gene. In such cases, it is natural to ask how the combined transcriptional response compares to the individual responses. The most commonly used mechanistic models predict additive or multiplicative combined responses, but a systematic genome-wide evaluation of these predictions is not available. Here, we analyzed the transcriptional response of human MCF-7 cells to retinoic acid and TGF-β, applied individually and in combination. The combined transcriptional responses of induced genes exhibited a range of behaviors, but clearly favored both additive and multiplicative outcomes. We performed paired chromatin accessibility measurements and found that increases in accessibility were largely additive. There was some association between super-additivity of accessibility and multiplicative or super-multiplicative combined transcriptional responses, while sub-additivity of accessibility associated with additive transcriptional responses. Our findings suggest that mechanistic models of combined transcriptional regulation must be able to reproduce a range of behaviors. Competing Interests: ES, BE, AC No competing interests declared, AR Receives consulting income and royalties related to Stellaris RNA FISH probes. (© 2020, Sanford et al.)
Databáze:	MEDLINE
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