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Buffering of Genetic Regulatory Networks in Drosophila melanogaster.

ABSTRACT: Regulatory variation in gene expression can be described by cis- and trans-genetic components. Here we used RNA-seq data from a population panel of Drosophila melanogaster test crosses to compare allelic imbalance (AI) in female head tissue between mated and virgin flies, an environmental change known to affect transcription. Indeed, 3048 exons (1610 genes) are differentially expressed in this study. A Bayesian model for AI, with an intersection test, controls type I error. There are ?200 genes with AI exclusively in mated or virgin flies, indicating an environmental component of expression regulation. On average 34% of genes within a cross and 54% of all genes show evidence for genetic regulation of transcription. Nearly all differentially regulated genes are affected in cis, with an average of 63% of expression variation explained by the cis-effects. Trans-effects explain 8% of the variance in AI on average and the interaction between cis and trans explains an average of 11% of the total variance in AI. In both environments cis- and trans-effects are compensatory in their overall effect, with a negative association between cis- and trans-effects in 85% of the exons examined. We hypothesize that the gene expression level perturbed by cis-regulatory mutations is compensated through trans-regulatory mechanisms, e.g., trans and cis by trans-factors buffering cis-mutations. In addition, when AI is detected in both environments, cis-mated, cis-virgin, and trans-mated-trans-virgin estimates are highly concordant with 99% of all exons positively correlated with a median correlation of 0.83 for cis and 0.95 for trans We conclude that the gene regulatory networks (GRNs) are robust and that trans-buffering explains robustness.

SUBMITTER: Fear JM

PROVIDER: S-EPMC4937466 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Buffering of Genetic Regulatory Networks in Drosophila melanogaster.

Fear Justin M JM León-Novelo Luis G LG Morse Alison M AM Gerken Alison R AR Van Lehmann Kjong K Tower John J Nuzhdin Sergey V SV McIntyre Lauren M LM

Genetics 20160518 3

Regulatory variation in gene expression can be described by cis- and trans-genetic components. Here we used RNA-seq data from a population panel of Drosophila melanogaster test crosses to compare allelic imbalance (AI) in female head tissue between mated and virgin flies, an environmental change known to affect transcription. Indeed, 3048 exons (1610 genes) are differentially expressed in this study. A Bayesian model for AI, with an intersection test, controls type I error. There are ∼200 genes ...[more]

PMID: 27194752

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Project description:Gene Regulatory Networks (GRNs) allow the study of regulation of gene expression of whole genomes. Among the most relevant advantages of using networks to depict this key process, there is the visual representation of large amounts of information and the application of graph theory to generate new knowledge. Nonetheless, despite the many uses of GRNs, it is still difficult and expensive to assign Transcription Factors (TFs) to the regulation of specific genes. ChIP-Seq allows the determination of TF Binding Sites (TFBSs) over whole genomes, but it is still an expensive technique that can only be applied one TF at a time and requires replicates to reduce its noise. Once TFBSs are determined, the assignment of each TF and its binding sites to the regulation of specific genes is not trivial, and it is often performed by carrying out site-specific experiments that are unfeasible to perform in all possible binding sites. Here, we addressed these relevant issues with a two-step methodology using Drosophila melanogaster as a case study. First, our protocol starts by gathering all transcription factor binding sites (TFBSs) determined with ChIP-Seq experiments available at ENCODE and FlyBase. Then each TFBS is used to assign TFs to the regulation of likely target genes based on the TFBS proximity to the transcription start site of all genes. In the final step, to try to select the most likely regulatory TF from those previously assigned to each gene, we employ GENIE3, a random forest-based method, and more than 9,000 RNA-seq experiments from D. melanogaster. Following, we employed known TF protein-protein interactions to estimate the feasibility of regulatory events in our filtered networks. Finally, we show how known interactions between co-regulatory TFs of each gene increase after the second step of our approach, and thus, the consistency of the TF-gene assignment. Also, we employed our methodology to create a network centered on the Drosophila melanogaster gene Hr96 to demonstrate the role of this transcription factor on mitochondrial gene regulation.

Dataset Information

Buffering of Genetic Regulatory Networks in Drosophila melanogaster.

Publications

Buffering of Genetic Regulatory Networks in Drosophila melanogaster.

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