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bioRxiv · 10.1101/2020.09.22.303438

Genes on Different Strands Mark Boundaries Associated with Co-regulation Domains

Baguette, A.·Bilodeau, S.·Bourque, G.
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Abstract

Gene regulation is influenced by chromatin conformation. Current models suggest that topologically associating domains (TADs) act as regulatory units, which could also include distinct co-expression domains (CODs) favouring correlated gene expression. We integrated publicly available RNA-seq, ChIP-seq and Hi-C data from A549 cells stimulated with the glucocorticoid dexamethasone to explore how differentially expressed genes are co-regulated among TADs and CODs. Interestingly, we found that gene position and orientation also impact co-regulation. Indeed, divergent and convergent pairs of genes we enriched at sub-TAD boundaries, forming distinct CODs. We also found that genes at COD boundaries were less likely to be separated by structural proteins such as Cohesin and CTCF. A complementary analysis of lung expression quantitative trait loci (eQTL) demonstrated that genes affected by the same variant were more likely to be found on the same strand while lacking a TAD boundary. Taken together, these results suggest a model where gene orientation can provide a boundary between CODs, at the sub-TAD level, thus affecting their likelihood of co-regulation.

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Baguette, A., Bilodeau, S., Bourque, G.. 2020-09-22. Genes on Different Strands Mark Boundaries Associated with Co-regulation Domains. https://doi.org/10.1101/2020.09.22.303438

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