High-resolution spatial multi-omics reveals cell-type specific nuclear compartments

Takei, Yodai; Yang, Yujing; White, Jonathan; Yun, Jina; Prasad, Meera; Ombelets, Lincoln J; Schindler, Simone; Cai, Long

doi:10.1101/2023.05.07.539762

Cited by 12 publications

(10 citation statements)

References 106 publications

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“…For example, both granule cells and Purkinje cells lack neuron-specific non-CpG DNA methylation ( 13 ), revealing that non-CpG methylation was neither required for our previously discovered neuron-specific radial genome movement ( 5 )—which we observed in both cell types (fig. S27) ( 36 )—nor required for suppressing ultra–long-range contacts.…”

Section: Discussionmentioning

confidence: 99%

Lifelong restructuring of 3D genome architecture in cerebellar granule cells

Tan,

Shi,

Moghadami

et al. 2023

Science

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The cerebellum contains most of the neurons in the human brain and exhibits distinctive modes of development and aging. In this work, by developing our single-cell three-dimensional (3D) genome assay—diploid chromosome conformation capture, or Dip-C—into population-scale (Pop-C) and virus-enriched (vDip-C) modes, we resolved the first 3D genome structures of single cerebellar cells, created life-spanning 3D genome atlases for both humans and mice, and jointly measured transcriptome and chromatin accessibility during development. We found that although the transcriptome and chromatin accessibility of cerebellar granule neurons mature in early postnatal life, 3D genome architecture gradually remodels throughout life, establishing ultra–long-range intrachromosomal contacts and specific interchromosomal contacts that are rarely seen in neurons. These results reveal unexpected evolutionarily conserved molecular processes that underlie distinctive features of neural development and aging across the mammalian life span.

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Section: Discussionmentioning

confidence: 99%

Lifelong restructuring of 3D genome architecture in cerebellar granule cells

Tan,

Shi,

Moghadami

et al. 2023

Science

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“…S32a, Supplementary Material online). Leveraging high-resolution genome-wide seqFISH+ imaging data in mESCs ( Takei et al 2023 ), we also observed a significant shorter mean spatial distance for retrocopy–parent pairs identified as colocalized by Hi-C in comparison with noncolocalized pairs ( P = 6.1 × 10 −94 ; supplementary fig. S33a, Supplementary Material online).…”

Section: Resultsmentioning

confidence: 64%

Interchromosomal Colocalization with Parental Genes Is Linked to the Function and Evolution of Mammalian Retrocopies

Yan,

Tian,

et al. 2023

Molecular Biology and Evolution

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Retrocopies are gene duplicates arising from reverse transcription of mature mRNA transcripts and their insertion back into the genome. While long being regarded as processed pseudogenes, more and more functional retrocopies have been discovered. How the stripped-down retrocopies recover expression capability and become functional paralogs continually intrigues evolutionary biologists. Here, we investigated the function and evolution of retrocopies in the context of 3D genome organization. By mapping retrocopy–parent pairs onto sequencing-based and imaging-based chromatin contact maps in human and mouse cell lines and onto Hi-C interaction maps in 5 other mammals, we found that retrocopies and their parental genes show a higher-than-expected interchromosomal colocalization frequency. The spatial interactions between retrocopies and parental genes occur frequently at loci in active subcompartments and near nuclear speckles. Accordingly, colocalized retrocopies are more actively transcribed and translated and are more evolutionarily conserved than noncolocalized ones. The active transcription of colocalized retrocopies may result from their permissive epigenetic environment and shared regulatory elements with parental genes. Population genetic analysis of retroposed gene copy number variants in human populations revealed that retrocopy insertions are not entirely random in regard to interchromosomal interactions and that colocalized retroposed gene copy number variants are more likely to reach high frequencies, suggesting that both insertion bias and natural selection contribute to the colocalization of retrocopy–parent pairs. Further dissection implies that reduced selection efficacy, rather than positive selection, contributes to the elevated allele frequency of colocalized retroposed gene copy number variants. Overall, our results hint a role of interchromosomal colocalization in the “resurrection” of initially neutral retrocopies.

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“…S32A). Leveraging high-resolution genome-wide seqFISH+ imaging data in mESCs (Takei et al 2023), we also observed a significant shorter mean spatial distance for retrocopy-parent pairs identified as colocalized by Hi-C in comparison with noncolocalized pairs (p = 6.1 × 10 -94 , supplementary fig. S33A).…”

Section: Colocalized Retrocopies Are More Likely To Be Functional And...mentioning

confidence: 66%

“…For two-layer seqFISH+ data in mESC (Takei et al 2023), we downloaded the physical coordinates (x, y, and z) of 100,049 genomic loci at 25-kb resolution in 1,076 cells from Zenodo (doi: 10.5281/zenodo.7693825). The spatial distance between any pair of loci binned at 200-kb resolution was calculated using the scripts provided by the authors (https://github.com/CaiGroup/dna-seqfish-plus-multi-omics).…”

Section: Methodsmentioning

confidence: 99%

Interchromosomal Colocalization with Parental Genes Is Linked to the Function and Evolution of Mammalian Retrocopies

Yan

Tian

et al. 2023

Preprint

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Retrocopies are gene duplicates arising from reverse transcription of mature mRNA transcripts and their insertion back into the genome. While long being regarded as processed pseudogenes, more and more functional retrocopies have been discovered. How the stripped-down retrocopies recover expression capability and become functional paralogs continually intrigues evolutionary biologists. Here, we investigated the function and evolution of retrocopies in the context of three-dimensional (3D) genome organization. By mapping retrocopy-parent pairs onto the chromatin contact maps of human and mouse cell lines, we found that retrocopies and their parental genes show a higher-than-expected interchromosomal colocalization frequency. The spatial interactions between retrocopies and parental genes occur frequently at loci in active subcompartments and near nuclear speckles. Accordingly, colocalized retrocopies are more actively transcribed and translated, and are more evolutionarily conserved than noncolocalized ones. The active transcription of colocalized retrocopies may result from their permissive epigenetic environment and shared regulatory elements with parental genes. Population genetic analysis on retroposed gene copy number variants (retroCNVs) in human populations revealed that retrocopy insertions are not entirely random in regard to interchromosomal interactions and that colocalized retroCNVs are more likely to reach high frequency, suggesting that both insertion bias and natural selection contribute to the colocalization of retrocopy-parent pairs. Further dissection implies that reduced selection efficacy, rather than positive selection, contributes to the elevated allele frequency of colocalized retroCNVs. Overall, our results hint a role of interchromosomal colocalization in the "resurrection" of initially neutral retrocopies.

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High-resolution spatial multi-omics reveals cell-type specific nuclear compartments

Cited by 12 publications

References 106 publications

Lifelong restructuring of 3D genome architecture in cerebellar granule cells

Lifelong restructuring of 3D genome architecture in cerebellar granule cells

Interchromosomal Colocalization with Parental Genes Is Linked to the Function and Evolution of Mammalian Retrocopies

Interchromosomal Colocalization with Parental Genes Is Linked to the Function and Evolution of Mammalian Retrocopies

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