Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Widespread contribution of transposable elements to the rewiring of mammalian 3D genomes

ABSTRACT: Transposable elements (TEs) are major contributors of genetic material in mammalian genomes. These often include binding sites for architectural proteins, including the multifarious master protein, CTCF, which shapes the 3D genome by creating loops, domains, compartment borders and RNA-DNA interactions, all of which play a role in the compact packaging of DNA and have the potential to facilitate regulatory function. In this study, we explore the widespread contribution of TEs to mammalian 3D genomes by quantifying the extent to which they give rise to loops and domain border differences across various cell types and species using several 3D genome mapping technologies. We show that specific (sub-)families of TEs have contributed to lineage-specific 3D chromatin structures across mammalian species. In many cases, these loops may facilitate interaction between distant cis-regulatory elements and target genes, and domains may segregate chromatin state to impact gene expression in a lineage-specific manner. An experimental validation of our analytical findings using CRISPR-Cas9 to delete a candidate TE resulted in disruption of species-specific 3D chromatin structure. Taken together, we comprehensively quantify and selectively validate our finding that TEs contribute to 3D genome organization and may, in some cases, impact gene regulation during the course of mammalian evolution.

ORGANISM(S): Homo sapiens

PROVIDER: GSE222526 | GEO | 2023/01/16

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

H4K16ac activates retrotransposons and contributes to their cis regulatory function [CUT&TAG]

Project description:Mammalian genomes harbour a large number of transposable elements (TEs) and their remnants. Most TEs are incapable of retrotransposition, however, they have evolved as cis-regulatory elements (CREs), enabling them to recruit host-encoded factors. Understanding the contribution of TEs in the regulation of the mammalian genome is an active area of research. Here we show that the male-specific lethal (MSL) complex-mediated acetylation of histone H4 lysine 16 (H4K16ac) regulates the transcription of TEs. Furthermore, H4K16ac marked TEs function as a rich source of cis regulatory elements in the human genome, wherein H4K16ac acts by maintaining the permissive chromatin structure and promoting the transcription of these TEs.

2023-04-13 | GSE200768 | GEO

H4K16ac activates retrotransposons and contributes to their cis regulatory function [ATAC-seq]

2023-04-13 | GSE200767 | GEO

H4K16ac activates retrotransposons and contributes to their cis regulatory function [RNA-seq]

2023-04-13 | GSE200769 | GEO

Epigenomic profiling of the innate immune response in bovine MDBK cells

Project description:Cattle are an important livestock species, and understanding the genomic architecture of agriculturally relevant traits such as disease susceptibility is of major interest in the bovine research community. Lineage-specific transposable elements (TEs) are a source of interferon-gamma (IFNG)-inducible regulatory elements that control human immune genes, but this possibility has been largely unexplored in other species that harbor distinct transposon landscapes, including cattle. We conducted transcriptomic and epigenomic profiling of the IFNG response in bovine cells, and found that ruminant-specific TEs are a major source of IFNG-inducible enhancer elements that shape bovine innate immune responses. CRISPR knockout experiments established that key immune genes including bovine IFNAR2 and IL2RB are regulated by TEs in MDBKs. Together with previous work in human cells, our findings demonstrate that lineage-specific TEs have been independently co-opted to regulate IFNG-inducible gene expression in at least two mammalian lineages. Therefore, TE co-option may mediate parallel evolutionary rewiring of mammalian immune regulation.

2021-10-02 | GSE185080 | GEO

Chromatin profiling of the innate immune response in bovine MDBK cells

2021-10-02 | GSE185079 | GEO

Transcriptional profiling of the innate immune response in bovine cells

2021-10-02 | GSE185081 | GEO

Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes

Project description:We recently used in situ Hi-C to create kilobase-resolution 3D maps of mammalian genomes. Here, we combine these with new Hi-C, microscopy, and genome-editing experiments to study the physical structure of chromatin fibers, domains, and loops. We find that the observed contact domains are inconsistent with the equilibrium state for an ordinary condensed polymer. Combining Hi-C data and novel mathematical theorems, we show that contact domains are also not consistent with a fractal globule. Instead, we use physical simulations to study two models of genome folding. In one, intermonomer attraction during polymer condensation leads to formation of an anisotropic "tension globule." In the other, CTCF and cohesin act together to extrude loops during interphase. Both models are consistent with the observed contact domains and with the observation that contact domains tend to form inside loops. However, the extrusion model explains a far wider array of observations, such as why loops tend not to overlap and why the CTCF-binding motifs at pairs of loop anchors lie in the convergent orientation. Finally, we perform 13 genome-editing experiments examining the effect of altering CTCF-binding sites on chromatin folding. The convergent rule correctly predicts the affected loop in every case. Moreover, the extrusion model accurately predicts in silico the 3D maps resulting from each experiment using only the location of CTCF-binding sites in the WT. Thus, we show that it is possible to disrupt, restore, and move loops and domains using targeted mutations as small as a single base pair. in situ Hi-C and HYbrid Capture Hi-C (Hi-C2) were used to probe the three-dimensional structure of the genome in two different human cell types before and after genome editing.

2015-10-23 | E-GEOD-74072 | biostudies-arrayexpress

CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function

Project description:CTCF/cohesin play a central role in insulator function and higher-order chromatin organization of mammalian genomes. Recent studies identified a correlation between the orientation of CTCF-binding sites (CBSs) and chromatin loops. To test the functional significance of this observation, we combined CRISPR/Cas9-based genomic-DNA-fragment editing with chromosome-conformation-capture experiments to show that the location and relative orientations of CBSs determine the specificity of long-range chromatin looping in mammalian genomes, using protocadherin (Pcdh) and β-globin as model genes. Inversion of CBS elements within the Pcdh enhancer reconfigures the topology of chromatin loops between the distal enhancer and target promoters, and alters gene-expression patterns. Thus, although enhancers can function in an orientation-independent manner in reporter assays, in the native chromosome context the orientation of at least some enhancers carrying CBSs can determine both the architecture of topological chromatin domains and enhancer/promoter specificity. The findings reveal how 3D chromosome architecture can be encoded by genome sequence.

2015-08-13 | GSE71275 | GEO

Epigenomic conservation of transposable element silencing [RNA-seq]

Project description:Transposable elements (TEs) comprise a substantial proportion of primate genomes. Because of the potential deleterious effects of TEs during development, TEs are targeted for silencing by sequence-specific KRAB-ZNF proteins, which recruit the TRIM28-SETDB1 complex, to deposit the repressive histone modification H3K9me3. TEs, in turn, acquire mutations to evade detection by the host, and hence KRAB-ZNF proteins need to rapidly evolve to counteract them. To investigate the short-term evolution of TE silencing, we profiled the genome-wide distribution of H3K9me3 in both human and chimpanzee induced pluripotent stem cells. We performed chromatin immunoprecipitation followed by high-throughput sequencing for H3K9me3, as well as total RNA sequencing in ten human and seven chimpanzee individuals. H3K9me3 enrichment was quantified in 141,642 regions determined to be orthologous between the two species. These H3K9me3-enriched regions were overlaid on a compiled set of 4 million orthologous TEs that can be mapped in both species.

2018-04-26 | GSE96711 | GEO

Epigenomic conservation of transposable element silencing [ChIP-seq]

2018-04-26 | GSE96710 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data