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

ABSTRACT: Signals often ultimately affect the transcription of genes, and often, two different signals can affect the transcription of the same gene. In such cases, it is natural to ask how the combined transcriptional response compares to the individual responses. Mechanistic models can predict a range of combined responses, with the most commonly applied models predicting additive or multiplicative responses, but systematic genome-wide evaluation of these predictions are not available. Here, we performed a comprehensive analysis of the transcriptional response of human MCF-7 cells to two different signals (retinoic acid and TGF-β), applied individually and in combination. We found that the combined responses exhibited a range of behaviors, but clearly favored both additive and multiplicative combined transcriptional responses. We also performed paired chromatin accessibility measurements to measure putative transcription factor occupancy at regulatory elements near these genes. We found that increases in chromatin accessibility were largely additive, meaning that the combined binding response was the sum of the binding responses to each signal individually. We found 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE152749 | GEO | 2020/06/19

REPOSITORIES: GEO

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Project description:The nuclear content of the plant endosperm is the result of the contribution two maternal genomes and a single paternal genome. This 2:1 dosage relationship provides a unique system for studying the additivity of gene expression levels in reciprocal hybrids. A combination of microarray profiling and allele-specific expression analysis was performed using RNA isolated from endosperm tissues of maize inbred lines B73 and Mo17 and their reciprocal hybrids at two developmental stages, 13 and 19 days after pollination. By assessing the relative levels of expression in the reciprocal hybrids it was possible to determine the prevalence of additive and non-additive expression patterns. While the majority of differentially expressed genes displayed additive expression patterns in the endosperm, approximately 10% of the genes displayed non-additive expression patterns including maternal-like, paternal-like, dominant high-parent, dominant low-parent and expression patterns outside the range of the inbreds. The frequency of hybrid expression patterns outside of the parental range in maize endosperm tissue is much higher than that observed for vegetative tissues. For a set of 90 genes allele-specific expression assays were employed to monitor allelic bias and regulatory variation. Eight of these genes exhibited evidence for maternally or paternally biased expression at multiple stages of endosperm development and are potential examples of differential imprinting. Collectively, our data indicate that parental effects on gene expression are much stronger in endosperm than in vegetative tissues, and that endosperm imprinting may be far more common than previously estimated. Experiment Overall Design: Affymetrix microarrays were used to perform expression profiling on 13 day after pollination endosperm tissue of four different genotypes; B73; Mo17, B73xMo17 and Mo17xB73. There are three biological replicates for each of the tissues. Each biological sample represents a pool containing 5 endosperms each, from 6 different ears.

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

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