Human transcriptional interactome of chromatin contribute to gene co-expression

Abstract

BackgroundTranscriptional interactome of chromatin is one of the important mechanisms in gene transcription regulation. By chromatin conformation capture and 3D FISH experiments, several chromatin interactions cases among sequence-distant genes or even inter-chromatin genes were reported. However, on genomics level, there is still little evidence to support these mechanisms. Recently based on Hi-C experiment, a genome-wide picture of chromatin interactions in human cells was presented. It provides a useful material for analysing whether the mechanism of transcriptional interactome is common.ResultsThe main work here is to demonstrate whether the effects of transcriptional interactome on gene co-expression exist on genomic level. While controlling the effects of transcription factors control similarities (TCS), we tested the correlation between Hi-C interaction and the mutual ranks of gene co-expression rates (provided by COXPRESdb) of intra-chromatin gene pairs. We used 6,084 genes with both TF annotation and co-expression information, and matched them into 273,458 pairs with similar Hi-C interaction ranks in different cell types. The results illustrate that co-expression is strongly associated with chromatin interaction. Further analysis using GO annotation reveals potential correlation between gene function similarity, Hi-C interaction and their co-expression.ConclusionsAccording to the results in this research, the intra-chromatin interactome may have relation to gene function and associate with co-expression. This study provides evidence for illustrating the effect of transcriptional interactome on transcription regulation.

Identifying Causal Genes at the Multiple Sclerosis Associated Region 6q23 Using Capture Hi-C

“…Intriguingly, these two separate regions, over 2.3Mb apart, interact with each other in T-cells but not B-cells ( S1 Fig ), suggesting that these pathways may converge to give rise to disease-specific MS mechanisms in a stimulus and cell type specific manner. In this regard, it has been previously shown that there is a correlation between chromatin interactions and gene co-expression [36–39] and it has been hypothesised that multiple co-regulated genes can interact and share regulatory elements at specialised ‘transcription factories‘ [16]. Our data possibly supports this idea and suggests a possible co-regulation of genes in this region in MS.…”

In the loop: promoter–enhancer interactions and bioinformatics

“…There is increasing support for PEIs being necessary for transcriptional regulation of an enhancer’s target gene. For example, there is evidence that the expression of a target gene is affected by gain or loss of competing promoters, lack of some PEI-associated proteins and addition of PEI-disrupting insulators [14], as well as evidence that chromatin interactions are highly associated to gene co-expression rates [15]. However, important challenges remain, such as finding the mechanisms that mediate PEIs, the building of high-resolution PEI maps in different cell types and the identification of functional interactions.…”

The Genome Conformation As an Integrator of Multi-Omic Data: The Example of Damage Spreading in Cancer

“…Evidences of the 3D genome conformation role in regulating and maintaining cellular functions are continuously emerging (Lieberman-Aiden et al, 2009; Dong et al, 2010; Schoenfelder et al, 2010; Gerstein et al, 2012; Kalhor et al, 2012; Lan et al, 2012; Shen et al, 2012; Homouz and Kudlicki, 2013; Jin et al, 2013; Papantonis and Cook, 2013; Babaei et al, 2015). For example, pathological genome organizations can be associated with many diseases, such as muscular dystrophy (Petrov et al, 2008) and Rett syndrome (Horike et al, 2005).…”