Co-regulation of paralog genes in the three-dimensional chromatin architecture
| Autor: | Jonas Ibn-Salem, Miguel A. Andrade-Navarro, Enrique M. Muro |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
animal structures Computational biology Biology Genome Chromosome conformation capture 03 medical and health sciences Mice 0302 clinical medicine Dogs Gene Duplication Gene duplication Genetics Animals Cluster Analysis Humans Promoter Regions Genetic Gene ChIA-PET Genomic organization Regulation of gene expression fungi Gene regulation Chromatin and Epigenetics Computational Biology Chromatin Assembly and Disassembly Biological Evolution Chromatin 030104 developmental biology Enhancer Elements Genetic Gene Expression Regulation 030217 neurology & neurosurgery |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 |
| Popis: | Paralog genes arise from gene duplication events during evolution, which often lead to similar proteins that cooperate in common pathways and in protein complexes. Consequently, paralogs show correlation in gene expression whereby the mechanisms of co-regulation remain unclear. In eukaryotes, genes are regulated in part by distal enhancer elements through looping interactions with gene promoters. These looping interactions can be measured by genome-wide chromatin conformation capture (Hi-C) experiments, which revealed self-interacting regions called topologically associating domains (TADs). We hypothesize that paralogs share common regulatory mechanisms to enable coordinated expression according to TADs. To test this hypothesis, we integrated paralogy annotations with human gene expression data in diverse tissues, genome-wide enhancer-promoter associations and Hi-C experiments in human, mouse and dog genomes. We show that paralog gene pairs are enriched for co-localization in the same TAD, share more often common enhancer elements than expected and have increased contact frequencies over large genomic distances. Combined, our results indicate that paralogs share common regulatory mechanisms and cluster not only in the linear genome but also in the three-dimensional chromatin architecture. This enables concerted expression of paralogs over diverse cell-types and indicate evolutionary constraints in functional genome organization. |
| Databáze: | OpenAIRE |
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