Variants in exons and in transcription factors affect gene expression in trans

Genome Biology

Itsik Pe'er¹  Anat Kreimer² 

[1] Department of Computer Science, Columbia University, 500 West 120th Street, New York, NY 10027, USA;Center of Computational Biology and Bioinformatics, Columbia University, New York, NY 10032, USA

关键词: transcriptome;    systems genetics;    systems biology;    regulatory networks;    regulation;    protein-protein-interaction networks;    eQTLs;    eSNPs;    Computational biology;   

Others  :  864154
DOI  :  10.1186/gb-2013-14-7-r71

 received in 2013-02-25, accepted in 2013-07-11,  发布年份 2013

【 摘 要 】

Background

In recent years many genetic variants (eSNPs) have been reported as associated with expression of transcripts in trans. However, the causal variants and regulatory mechanisms through which they act remain mostly unknown. In this paper we follow two kinds of usual suspects: SNPs that alter coding regions or transcription factors, identifiable by sequencing data with transcriptional profiles in the same cohort. We show these interpretable genomic regions are enriched for eSNP association signals, thereby naturally defining source-target gene pairs. We map these pairs onto a protein-protein interaction (PPI) network and study their topological properties.

Results

For exonic eSNP sources, we report source-target proximity and high target degree within the PPI network. These pairs are more likely to be co-expressed and the eSNPs tend to have a cis effect, modulating the expression of the source gene. In contrast, transcription factor source-target pairs are not observed to have such properties, but instead a transcription factor source tends to assemble into units of defined functional roles along with its gene targets, and to share with them the same functional cluster of the PPI network.

Conclusions

Our results suggest two modes of trans regulation: transcription factor variation frequently acts via a modular regulation mechanism, with multiple targets that share a function with the transcription factor source. Notwithstanding, exon variation often acts by a local cis effect, delineating shorter paths of interacting proteins across functional clusters of the PPI network.

【 授权许可】

   
2013 Kreimer and Pe'er; licensee BioMed Central Ltd.

【 图 表 】

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