Making sense of the linear genome, gene function and TADs

Journal article

The advent of Chromosome Conformation Capture (3C) assays, particularly Hi-C, have revolutionized our understanding of three-dimensional (3D) genome organization. 3D genomic structures play crucial roles in gene regulation, cellular division, and embryonic development, and show evolutionary conservation across species. Although the 3D genome has primarily been studied in humans and select model species of mammals, 3D organization can vary between species. Consequently, our understanding of 3D genome organization in other species remains limited. This thesis aims to perform the first general characterization of 3D chromatin structures in the non-model species Atlantic salmon (Salmo salar), focusing on compartments and topologically associating domains (TADs). Atlantic salmon has also undergone a relatively recent whole genome duplication (WGD). The sub aim is therefore to assess the impact of WGD on 3D genome organization and regulatory evolution. By combining Hi-C data with RNA-seq and ATAC-seq, we characterized the 3D genome landscape in Atlantic salmon liver, and the connection to gene regulation. Our analyses revealed similarities with established 3D structures and their gene regulatory roles, albeit with a notably lower presence of CTCF at TAD boundaries compared to many studies in mammals, challenging the causal link between TAD formation and CTCF proteins. Additionally, we established associations between compartmentalization and gene expression patterns in duplicated regions post-WGD, suggesting the involvement of 3D chromatin structures in the expression divergence of duplicated genes. While selection on transcript dosage merge as a possible driver for this, understanding selective pressures on genomic 3D organization remains an ongoing topic of investigation. Furthermore, our findings challenge the expected correlations between TAD metrics (gene content similarity and TAD strength) and gene expression levels in duplicated regions. In conclusion, this study advances our general understanding of 3D genomic architecture across the tree of life, and specifically in Atlantic salmon. Furthermore, it sheds light on the role of 3D genome organization in genome evolution following a WGD

Authors: Long, HS; Greenaway, S; Powell, G; Mallon, A-M; Lindgren, CM

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: BioMed Central
• Journal: Epigenetics & Chromatin
• Volume: 15
• Issue: 1
• Pages: 4-4
• Article number: 4
• Publication date: 2022-01-28
• DOI: 10.1186/s13072-022-00436-9
• EISSN: 1756-8935
• ISSN: 1756-8935
• Language: English
• Keywords: Chromatin; CTCF; Gene; Enhancer; Genome; Function (biology); Biology; Constraint (computer-aided design); Mathematics; Transcription factor; Genetics; Computational biology