Topologically associated domains: a successful scaffold for the evolution of gene regulation in animals

Abstract Background Our understanding of genome regulation is ever-evolving with the continuous discovery of new modes of gene regulation, and transcriptomic studies of mammalian genomes have revealed the presence of a considerable population of non-coding RNA molecules among the transcripts expressed. One such non-coding RNA molecule is long non-coding RNA (lncRNA). However, the function of lncRNAs in gene regulation is not well understood; moreover, finding conserved lncRNA across species is a challenging task. Therefore, we propose a novel approach to identify conserved lncRNAs and functionally annotate these molecules. Results In this study, we exploited existing myogenic transcriptome data and identified conserved lncRNAs in mice and humans. We identified the lncRNAs expressing differentially between the early and later stages of muscle development. Differential expression of these lncRNAs was confirmed experimentally in cultured mouse muscle C2C12 cells. We utilized the three-dimensional architecture of the genome and identified topologically associated domains for these lncRNAs. Additionally, we correlated the expression of genes in domains for functional annotation of these trans-lncRNAs in myogenesis. Using this approach, we identified conserved lncRNAs in myogenesis and functionally annotated them. Conclusions With this novel approach, we identified the conserved lncRNAs in myogenesis in humans and mice and functionally annotated them. The method identified a large number of lncRNAs are involved in myogenesis. Further studies are required to investigate the reason for the conservation of the lncRNAs in human and mouse while their sequences are dissimilar. Our approach can be used to identify novel lncRNAs conserved in different species and functionally annotated them.

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Evolution of gene regulation between ascidian species

Mechanisms of Development ◽

10.1016/j.mod.2017.04.287 ◽

2017 ◽

Vol 145 ◽

pp. S108-S109

Author(s):

Alicia Madgwick ◽

Damien Gailly ◽

Marta Silvia Magri ◽

José-Luis Gomez-Skarmeta ◽

Patrick Lemaire

Keyword(s):

Gene Regulation ◽

Ascidian Species ◽

Evolution Of Gene Regulation

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Topologically associated domains enriched for lineage-specific genes reveal expression-dependent nuclear topologies during myogenesis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1521826113 ◽

2016 ◽

Vol 113 (12) ◽

pp. E1691-E1700 ◽

Cited By ~ 27

Author(s):

Daniel S. Neems ◽

Arturo G. Garza-Gongora ◽

Erica D. Smith ◽

Steven T. Kosak

Keyword(s):

Gene Regulation ◽

Genome Organization ◽

Spatial Organization ◽

Potential Role ◽

Spatial Distance ◽

Linear Distribution ◽

Myotube Formation ◽

Topologically Associated Domains ◽

The Relationship ◽

Lineage Specific Genes

The linear distribution of genes across chromosomes and the spatial localization of genes within the nucleus are related to their transcriptional regulation. The mechanistic consequences of linear gene order, and how it may relate to the functional output of genome organization, remain to be fully resolved, however. Here we tested the relationship between linear and 3D organization of gene regulation during myogenesis. Our analysis has identified a subset of topologically associated domains (TADs) that are significantly enriched for muscle-specific genes. These lineage-enriched TADs demonstrate an expression-dependent pattern of nuclear organization that influences the positioning of adjacent nonenriched TADs. Therefore, lineage-enriched TADs inform cell-specific genome organization during myogenesis. The reduction of allelic spatial distance of one of these domains, which contains Myogenin, correlates with reduced transcriptional variability, identifying a potential role for lineage-specific nuclear topology. Using a fusion-based strategy to decouple mitosis and myotube formation, we demonstrate that the cell-specific topology of syncytial nuclei is dependent on cell division. We propose that the effects of linear and spatial organization of gene loci on gene regulation are linked through TAD architecture, and that mitosis is critical for establishing nuclear topologies during cellular differentiation.

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Evolution of Gene Regulation: Hybrid Networks Breed Diversity

Current Biology ◽

10.1016/j.cub.2012.10.026 ◽

2012 ◽

Vol 22 (23) ◽

pp. R1009-R1011

Author(s):

Andrea I. Ramos ◽

Scott Barolo

Keyword(s):

Gene Regulation ◽

Hybrid Networks ◽

Evolution Of Gene Regulation

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Evolution of gene regulation

Physics Today ◽

10.1063/pt.4.0669 ◽

2009 ◽

Keyword(s):

Gene Regulation ◽

Evolution Of Gene Regulation

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Coexpression reveals conserved mechanisms of transcriptional cell identity

10.1101/2020.11.10.375758 ◽

2020 ◽

Cited By ~ 1

Author(s):

Megan Crow ◽

Hamsini Suresh ◽

John Lee ◽

Jesse Gillis

Keyword(s):

Gene Regulation ◽

Cell Types ◽

Regulatory Evolution ◽

Closely Related Species ◽

Cell Identity ◽

Gene Coexpression ◽

Evolution Of Gene Regulation ◽

Orthology Prediction ◽

Species Specific ◽

Coexpression Networks

ABSTRACTWhat makes a mouse a mouse, and not a hamster? The answer lies in the genome, and more specifically, in differences in gene regulation between the two organisms: where and when each gene is expressed. To quantify differences, a typical study will either compare functional genomics data from homologous tissues, limiting the approach to closely related species; or compare gene repertoires, limiting the resolution of the analysis to gross correlations between phenotypes and gene family size. As an alternative, gene coexpression networks provide a basis for studying the evolution of gene regulation without these constraints. By incorporating data from hundreds of independent experiments, meta-analytic coexpression networks reflect the convergent output of species-specific transcriptional regulation.In this work, we develop a measure of regulatory evolution based on gene coexpression. Comparing data from 14 species, we quantify the conservation of coexpression patterns 1) as a function of evolutionary time, 2) across orthology prediction algorithms, and 3) with reference to cell- and tissue-specificity. Strikingly, we uncover deeply conserved patterns of gradient-like expression across cell types from both the animal and plant kingdoms. These results suggest that ancient genes contribute to transcriptional cell identity through mechanisms that are independent of duplication and divergence.

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Sea anemone genomes reveal ancestral metazoan chromosomal macrosynteny

10.21203/rs.3.rs-796229/v1 ◽

2021 ◽

Author(s):

Ulrich Technau ◽

Sophia Robb ◽

Grigory Genikhovich ◽

Juan Montenegro ◽

Witney Fropf ◽

...

Keyword(s):

Gene Regulation ◽

Draft Genome ◽

Gene Clusters ◽

Sea Anemone ◽

Gene Repertoire ◽

Sea Anemones ◽

Animal Evolution ◽

Topologically Associated Domains ◽

Genome Assemblies ◽

Chromosome Level

Abstract Draft genome sequences of non-bilaterian species have provided important insights into the evolution of the metazoan gene repertoire. However, there is little information about the evolution of gene clusters, genome architectures and karyotypes during animal evolution. Here we report chromosome-level genome assemblies of two related anthozoan cnidarians, the sea anemones, Nematostella vectensis and Scolanthus callimorphus. We find a robust set of 15 chromosomes with a clear one-to-one correspondence of the chromosomes between the two species. We show that, in contrast to Bilateria, Hox and NK clusters of investigated cnidarians are disintegrated, indicating that microsynteny conservation is largely lost. In line with that, we find no evidence for topologically associated domains, suggesting fundamental difference in long-range gene regulation compared to vertebrates. However, both sea anemone genomes show remarkable chromosomal conservation with other cnidarians, several bilaterians and the sponge Ephydatia muelleri, allowing us to reconstruct the putative cnidarian and metazoan chromosomes, consisting of 19 and 16 ancestral linkage groups, respectively. These data suggest that large parts of the ancestral metazoan genome have been retained in chromosomes of some extant lineages, yet, higher order gene regulation may have evolved only after the cnidarian-bilaterian split.

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