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

Abstract:

: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.

journal_name

Elife

journal_title

eLife

authors

Sanford EM,Emert BL,Coté A,Raj A

doi

10.7554/eLife.59388

subject

Has Abstract

pub_date

2020-12-07 00:00:00

issn

2050-084X

pii

59388

journal_volume

9

pub_type

杂志文章

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