Lefebvre, V.; Foissac, S.; Djebali, S.; Necsulea, A.

In multicellular organisms, gene expression is controlled by numerous cis-regulatory elements that can be located far away from their target genes on the linear genome. Interactions between gene promoters and distant regulatory elements take place through chromatin contacts or loops. While other aspects of gene expression regulation have been well studied, regulatory chromatin contact evolution remains largely unexplored, due to a lack of comparable data across species. Here, we study the evolution of regulatory chromatin contacts by focusing on duplicated genes in the mouse genome. We use an extensive collection of high resolution promoter-centered Hi-C data to define promoter-enhancer chromatin contacts for 1,420 pairs of duplicated genes and to study their evolutionary divergence, in conjunction with the evolutionary divergence of their expression patterns. We show that chromatin contacts evolve faster than expression patterns, as previously observed for other gene regulation mechanisms. We show that duplicated gene localisation cis or in trans is strongly associated with chromatin contact divergence. We find a significant correlation between expression divergence and chromatin contact divergence across duplicated gene pairs. Our results highlight the complex evolutionary dynamics of regulatory chromatin contacts, as well as its relationship with gene expression evolution, across a broad time scale.