Comparative 3D Genome Architecture in Vertebrates
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA704983 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13786600_1.fastq.gz | Fastqsanger.gz | |||
| SRR13786600_2.fastq.gz | Fastqsanger.gz | |||
| SRR13786601_1.fastq.gz | Fastqsanger.gz | |||
| SRR13786601_2.fastq.gz | Fastqsanger.gz | |||
| SRR13786602_1.fastq.gz | Fastqsanger.gz |
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Project description:Three-dimensional genome architecture influences the regulation of essential nuclear processes, such as gene transcription. However, how 3D genome architecture is affected by evolutionary forces within major lineages remains unclear. Here, we report a comprehensive comparison of 3D genomes, using high resolution Hi-C data in fibroblast cells of fish, chickens, and 10 mammalian species. This analysis shows a correlation between genome size and chromosome length that affects chromosomal territory (CT) organization in the upper hierarchy of genome architecture, whereas lower hierarchical features, including local transcriptional availability of DNA, are selected through vertebrate’s evolution. Further, conservation of topologically associating domains (TADs) appears strongly associated with the modularity of expression profiles across species. Additionally, LINE and SINE transposable elements likely contribute to heterochromatin and euchromatin organization, respectively, during the evolution of genome architecture. These findings can guide ongoing investigations of genome evolution by extending our understanding of the mechanisms shaping genome architecture.
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Project description:Three-dimensional genome architecture influences the regulation of essential nuclear processes, such as gene transcription. However, how 3D genome architecture is affected by evolutionary forces within major lineages remains unclear. Here, we report a comprehensive comparison of 3D genomes, using high resolution Hi-C data in fibroblast cells of fish, chickens, and 10 mammalian species. This analysis shows a correlation between genome size and chromosome length that affects chromosomal territory (CT) organization in the upper hierarchy of genome architecture, whereas lower hierarchical features, including local transcriptional availability of DNA, are selected through vertebrate’s evolution. Further, conservation of topologically associating domains (TADs) appears strongly associated with the modularity of expression profiles across species. Additionally, LINE and SINE transposable elements likely contribute to heterochromatin and euchromatin organization, respectively, during the evolution of genome architecture. These findings can guide ongoing investigations of genome evolution by extending our understanding of the mechanisms shaping genome architecture.
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Project description:Vision depends on the functional interplay between the photoreceptor cells of the neural retina and the supporting cells of the underlying retinal pigment epithelium (RPE). Many genes involved in inherited retinal diseases (IRD) display highly specific spatiotemporal expression within these interconnected retinal components through the local recruitment of cis-regulatory elements (CREs) in 3D nuclear space. To understand the role of differential chromatin architecture in establishing tissue-specific expression patterns at IRD loci in the human neural retina and the RPE, we mapped genome-wide chromatin interactions by applying in situ Hi-C and H3K4me3 HiChIP to human adult post-mortem donor retinas. A comparative 3D genome analysis between neural retina and RPE revealed that almost 60% of known IRD genes were marked by differential cis-regulatory interactions or 3D genome structure. Furthermore, we zoomed in on tissue-specific chromatin interactions at the ABCA4 locus, which is implicated in the most common autosomal recessive IRD. We constructed high-resolution ABCA4 interaction profiles using UMI-4C, which, upon integration with bulk and single-cell epigenomic datasets and in vivo enhancer assays in zebrafish, revealed tissue-specific CREs for ABCA4. In summary, through extensive comparative 3D genome mapping, based on genome-wide (Hi-C), promoter-centric (HiChIP) and locus-specific (UMI-4C) assays of human neural retina and RPE, we have shown that gene regulation at key IRD loci is likely mediated by tissue-specific chromatin interactions. These findings do not only provide insight into tissue-specific regulatory landscapes at retinal disease loci, but also delineate the search space for genomic variation underlying unsolved IRD.
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