Sep 17, 2015

A pathway-centric view of spatial proximity in the 3D nucleome across cell lines

BioRxiv : the Preprint Server for Biology
Hiren KarathiaSridhar Hannenhalli

Abstract

Spatial organization of the genome is critical for condition-specific gene expression. Previous studies have shown that functionally related genes tend to be spatially proximal. However, these studies have not been extended to multiple human cell types, and the extent to which context-specific spatial proximity of a pathway is related to its context-specific activity is not known. We report the first pathway-centric analyses of spatial proximity in six human cell lines. We find that spatial proximity of genes in a pathway tends to be context-specific, in a manner consistent with the pathway's context-specific expression and function; housekeeping genes are ubiquitously proximal to each other, and cancer-related pathways such as p53 signaling are uniquely proximal in hESC. Intriguingly, we find a correlation between the spatial proximity of genes and interactions of their protein products, even after accounting for the propensity of co-pathway proteins to interact. Related pathways are also often spatially proximal to one another, and housekeeping genes tend to be proximal to several other pathways suggesting their coordinating role. Further, the spatially proximal genes in a pathway tend to be the drivers of the pathway activit...Continue Reading

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Mentioned in this Paper

Study
Biochemical Pathway
Genome
Genes
Three-dimensional
Cell to Cell Adhesion Signaling Pathway
Transcription, Genetic
Gene Expression
TP53
Human Cell Line

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