Evolutionary comparison reveals that diverging CCCTC-binding factor (CTCF) sites are signatures of ancestral topological associating domains borders
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Strongylocentrotus purpuratus Danio rerio
PROVIDER: GSE66900 | GEO | 2015/05/18
SECONDARY ACCESSION(S): PRJNA278402
REPOSITORIES: GEO
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Project description:Comparison of conserved TAD boundaries reveals that diverging CTCF sites is an evolutionary conserved signature associated with TAD borders 4C-seq samples for six gene family promoters in different samples: E9.5 and E14.5 mouse embryos ; 24hpf, 48hpf, 80%epiboly and Dome zebrafish embryos ; 48hpf S.purpuratus embryos
2015-05-18 | E-GEOD-66900 | biostudies-arrayexpress
Project description:Evolutionary comparison reveals that diverging CCCTC-binding factor (CTCF) sites are signatures of ancestral topological associating domains borders
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Project description:Increasing evidence in the last years indicates that the vast amount of regulatory information contained in mammalian genomes is organized in precise 3D chromatin structures. However, the impact of this spatial chromatin organization on gene expression and its degree of evolutionary conservation is still poorly understood. The Six homeobox genes are essential developmental regulators organized in gene clusters conserved during evolution. Here, we reveal that the Six clusters share a deeply evolutionarily conserved 3D chromatin organization that predates the Cambrian explosion. This chromatin architecture generates two largely independent regulatory landscapes (RLs) contained in two adjacent topological associating domains (TADs). By disrupting the conserved TAD border in one of the zebrafish Six clusters, we demonstrate that this border is critical for preventing competition between promoters and enhancers located in separated RLs, thereby generating different expression patterns in genes located in close genomic proximity. Moreover, evolutionary comparison of Six-associated TAD borders reveals the presence of CCCTC-binding factor (CTCF) sites with diverging orientations in all studied deuterostomes. Genome-wide examination of mammalian HiC data reveals that this conserved CTCF configuration is a general signature of TAD borders, underscoring that common organizational principles underlie TAD compartmentalization in deuterostome evolution.
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Project description:Genome organization is driven by forces affecting transcriptional state, but the relationship between transcription and genome architecture remains unclear. Here, we identified the Drosophila transcription factor Motif 1 Binding Protein (M1BP) in physical association with the gypsy chromatin insulator core complex, including the universal insulator protein CP190. M1BP is required for enhancer-blocking and barrier activities of the gypsy insulator as well as its proper nuclear localization. Genome-wide, M1BP specifically colocalizes with CP190 at Motif 1-containing promoters, which are enriched at topologically associating domain (TAD) borders. M1BP facilitates CP190 chromatin binding at many shared sites and vice versa. Both factors promote Motif 1-dependent gene expression and transcription near TAD borders genome-wide. Finally, loss of M1BP reduces chromatin accessibility and increases both inter- and intra-TAD local genome compaction. Our results reveal physical and functional interaction between CP190 and M1BP to activate transcription at TAD borders and mediate chromatin insulator-dependent genome organization.
2021-06-07 | PXD026497 | Pride
Project description:Genome organization is driven by forces affecting transcriptional state, but the relationship between transcription and genome architecture remains unclear. Here, we identified the Drosophila transcription factor Motif 1 Binding Protein (M1BP) in physical association with the gypsy chromatin insulator core complex, including the universal insulator protein CP190. M1BP is required for enhancer-blocking and barrier activities of the gypsy insulator as well as its proper nuclear localization. Genome-wide, M1BP specifically colocalizes with CP190 at Motif 1-containing promoters, which are enriched at topologically associating domain (TAD) borders. M1BP is required for CP190 chromatin binding at many shared sites, and CP190 also affects M1BP chromatin association. Both factors are required for Motif 1-dependent gene expression and transcription near TAD borders genome-wide. Finally, loss of M1BP alters local genome compaction. Our results reveal physical and functional interaction between CP190 and M1BP to activate transcription at TAD borders and mediate chromatin insulator-dependent genome organization.
2021-04-14 | GSE169105 | GEO
Project description:Eukaryotic genomes are structurally organized via the formation of multiple loops that create gene expression regulatory units called topologically associating domains (TADs). Here we revealed the KSHV TAD structure at 500 base pair resolution and constructed a 3D KSHV genomic structural model. The latent KSHV genome formed very similar TAD structures among three different naturally infected PEL cell lines. When KSHV reactivation was triggered, genomic loops within TADs were dramatically decreased, while contacts extending outside of TAD borders increased, leading to formation of a larger regulatory unit with a shift from repressive to active compartments (B to A). The 3D structural model proposes that the immediate-early promoter region is localized on the periphery of the 3D viral genome, while highly inducible non-coding RNA regions moved toward the inner space of the structure, resembling the coordination of a "bird cage" during reactivation. Finally, inhibition of the initial burst of lytic gene expression by stop codon insertion in the viral transactivator reduced genomic loops, while supplementing K-Rta expression in trans during establishment of latency attenuated the defect. Our studies suggest that the latent 3D genomic structural information is embedded in the lytic gene transcription program.
2022-06-25 | GSE163696 | GEO
Project description:The DNA in humans and many animals is compartmentalised in topologically associating domains (TADs). In Drosophila, several architectural proteins are enriched at TAD borders, but we are still missing evidence that these proteins have a functional role in TAD maintenance. Here, we show that depletion of BEAF-32, Cp190 and Chro leads to changes in TAD organisation and chromatin loops. Their depletion affects mainly TAD borders in heterochromatin, while euchromatin TAD borders are resilient to these mutants. Furthermore, transcriptomic data identified thousands of genes displaying differential expression in these mutants and that majority of differentially expressed genes are in TADs that are reorganised. In contrast, we observed a lower effect on gene expression by the loss of chromatin loops. Our work identified for the first time a functional role for architectural proteins at TAD borders in Drosophila and a strong link between TAD reorganisation and changes in gene expression.
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Project description:Recent advances enabled by Hi-C technique have unraveled principles of chromosomal folding, which were since linked to many genomic processes. In particular, Hi-C revealed that chromosomes of animals are organized into Topologically Associating Domains (TADs), evolutionary conserved compact chromatin domains that influence gene expression. However, mechanisms that underlie partitioning of the genome into TADs remain poorly understood. To explore principals of TAD folding in Drosophila melanogaster, we performed Hi-C and PolyA+ RNA-seq in four cell lines of various origins (S2, Kc167, DmBG3-c2, and OSC). Contrary to previous studies, we find that regions between TADs (i.e. the inter-TADs and TAD boundaries) in Drosophila are only weakly enriched with the insulator protein dCTCF, while another insulator protein Su(Hw) is preferentially present within TADs. However, Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes. Accordingly, we find that binding of insulator proteins dCTCF and Su(Hw) predict TAD boundaries much worse than the active chromatin marks (in the minimal case, H3K4me3 and total RNA) do. Moreover, inter-TADs correspond to decompacted interbands of polytene chromosomes, whereas TADs mostly correspond to densely packed bands. Collectively, our results suggest that TADs are condensed chromatin domains depleted in active chromatin marks, separated by regions of active chromatin that cannot be organized into compact structures, possibly due to high levels of histone acetylation. Finally, we test this hypothesis by polymer simulations, and find that TAD partitioning can be explained by different modes of inter-nucleosomal interactions for active and inactive chromatin. Hi-C experiments, PolyA+ RNA profiling and mapping of chromosomal rearrangements in four Drosophila melanogaster cell lines.
2015-10-26 | E-GEOD-69013 | biostudies-arrayexpress
Project description:Chromosomes of metazoan organisms are partitioned in the interphase nucleus into discrete topologically associating domains (TADs). Borders between TADs are preferentially formed in regions containing high density of active genes and clusters of architectural protein binding sites. Transcription of most genes is turned off during the heat shock response in Drosophila. Here we show that temperature stress induces relocalization of architectural proteins from TAD borders to inside TADs, and this is accompanied by a dramatic rearrangement in the 3D organization of the nucleus. TAD border strength declines, allowing for an increase in long-distance inter-TAD interactions. Similar but quantitatively weaker effects are observed upon inhibition of transcription or depletion of individual architectural proteins. New heat shock-induced inter-TAD interactions result in increased contacts among enhancers and promoters of silenced genes, which recruit Pc and form Pc bodies at the nucleolus. These results suggest that the TAD organization of metazoan genomes is plastic and can be quickly reconfigured to allow new interactions between distant sequences. Analysis of the distribution of architectural proteins, chromatin proteins and histone modifications in Drosophila Kc167 cells. Cells were grown at 25 C (NT) or heat shocked for 20 min at 36.5 C (HS). Both control and reference samples are included. For some of the samples, replicates are also included.
2015-02-24 | E-GEOD-62904 | biostudies-arrayexpress
Project description:In the fetal mouse testis, PIWI Interacting RNAs (piRNAs) guide PIWI proteins to silence transposons, but after birth, most post-pubertal pachytene piRNAs map to genome uniquely and are thought to regulate genes required for male fertility. In human males, the developmental classes, precise genomic origins, and transcriptional regulation of post-natal piRNAs remain undefined. Here, we demarcate the genes and transcripts that produce post-natal piRNAs in human juvenile and adult testes. As in mouse, A‑MYB in humans drives transcription of both pachytene piRNA precursor transcripts and the mRNAs encoding piRNA biogenesis factors. Although human piRNA genes are syntenic to those in other placental mammals, their sequences are poorly conserved. In fact, pachytene piRNA loci are rapidly diverging even among modern humans. Our findings suggest that during mammalian evolution, pachytene piRNA genes are under fewer selective constraints. We speculate that pachytene piRNA diversity may provide a hitherto unrecognized driver of reproductive isolation.
2019-12-23 | GSE135791 | GEO