Similar Datasets
Project description:Trimethylation of histone H3 lysine 9 (H3K9me3) is critical for regulation of gene repression and heterochromatin formation, cell-fate determination, and organismal development. In particular, H3K9me3 provides an essential mechanism for silencing various transposon elements (TEs). However, previous studies showed that the canonical H3K9me3 readers (e.g. HP1 and MPP8) play rather limited roles in silencing endogenous retroviruses (ERVs), one of major TE classes in the mammalian genome. Here, we report that Trinucleotide Repeat Containing 18 (TNRC18), a previously under-studied chromatin regulator, recognizes H3K9me3 and directly binds ERVs, mediating ERV silencing. Our biochemical, biophysical and structural studies identified the C-terminal Bromo Adjacent Homology (BAH) domain of TNRC18 (TNRC18BAH) as a H3K9me3-specific reader, and its N-terminal segment as a platform for direct recruitment of co-repressors such as TRIM28 and HDAC-Sin3-NCoR complexes, thereby enforcing optimal repression of the H3K9me3-demarcated ERVs. Point mutagenesis that disrupts the TNRC18BAH-mediated H3K9me3 engagement caused neonatal lethality in mice and, in multiple mammalian cell models, led to de-repressed expression of ERVs, affecting the landscape of cis-regulatory elements and thus gene-expression programs. Collectively, this study describes a previously-unknown TNRC18BAH-directed H3K9me3-sensing pathway, which operates to epigenetically silence the evolutionarily young ERVs, thereby exerting profound impacts on host genome integrity, transcriptomic regulation, immunity, and development.
2023-07-24 | GSE233830 | GEO
Project description:Trimethylation of histone H3 lysine 9 (H3K9me3) is critical for regulation of gene repression and heterochromatin formation, cell-fate determination, and organismal development. In particular, H3K9me3 provides an essential mechanism for silencing various transposon elements (TEs). However, previous studies showed that the canonical H3K9me3 readers (e.g. HP1 and MPP8) play rather limited roles in silencing endogenous retroviruses (ERVs), one of major TE classes in the mammalian genome. Here, we report that Trinucleotide Repeat Containing 18 (TNRC18), a previously under-studied chromatin regulator, recognizes H3K9me3 and directly binds ERVs, mediating ERV silencing. Our biochemical, biophysical and structural studies identified the C-terminal Bromo Adjacent Homology (BAH) domain of TNRC18 (TNRC18BAH) as a H3K9me3-specific reader, and its N-terminal segment as a platform for direct recruitment of co-repressors such as TRIM28 and HDAC-Sin3-NCoR complexes, thereby enforcing optimal repression of the H3K9me3-demarcated ERVs. Point mutagenesis that disrupts the TNRC18BAH-mediated H3K9me3 engagement caused neonatal lethality in mice and, in multiple mammalian cell models, led to de-repressed expression of ERVs, affecting the landscape of cis-regulatory elements and thus gene-expression programs. Collectively, this study describes a previously-unknown TNRC18BAH-directed H3K9me3-sensing pathway, which operates to epigenetically silence the evolutionarily young ERVs, thereby exerting profound impacts on host genome integrity, transcriptomic regulation, immunity, and development.
2023-07-24 | GSE205505 | GEO
Project description:Trimethylation of histone H3 lysine 9 (H3K9me3) is critical for regulation of gene repression and heterochromatin formation, cell-fate determination, and organismal development. In particular, H3K9me3 provides an essential mechanism for silencing various transposon elements (TEs). However, previous studies showed that the canonical H3K9me3 readers (e.g. HP1 and MPP8) play rather limited roles in silencing endogenous retroviruses (ERVs), one of major TE classes in the mammalian genome. Here, we report that Trinucleotide Repeat Containing 18 (TNRC18), a previously under-studied chromatin regulator, recognizes H3K9me3 and directly binds ERVs, mediating ERV silencing. Our biochemical, biophysical and structural studies identified the C-terminal Bromo Adjacent Homology (BAH) domain of TNRC18 (TNRC18BAH) as a H3K9me3-specific reader, and its N-terminal segment as a platform for direct recruitment of co-repressors such as TRIM28 and HDAC-Sin3-NCoR complexes, thereby enforcing optimal repression of the H3K9me3-demarcated ERVs. Point mutagenesis that disrupts the TNRC18BAH-mediated H3K9me3 engagement caused neonatal lethality in mice and, in multiple mammalian cell models, led to de-repressed expression of ERVs, affecting the landscape of cis-regulatory elements and thus gene-expression programs. Collectively, this study describes a previously-unknown TNRC18BAH-directed H3K9me3-sensing pathway, which operates to epigenetically silence the evolutionarily young ERVs, thereby exerting profound impacts on host genome integrity, transcriptomic regulation, immunity, and development.
2023-07-24 | GSE200837 | GEO
Project description:Trimethylation of histone H3 lysine 9 (H3K9me3) is critical for regulation of gene repression and heterochromatin formation, cell-fate determination, and organismal development. In particular, H3K9me3 provides an essential mechanism for silencing various transposon elements (TEs). However, previous studies showed that the canonical H3K9me3 readers (e.g. HP1 and MPP8) play rather limited roles in silencing endogenous retroviruses (ERVs), one of major TE classes in the mammalian genome. Here, we report that Trinucleotide Repeat Containing 18 (TNRC18), a previously under-studied chromatin regulator, recognizes H3K9me3 and directly binds ERVs, mediating ERV silencing. Our biochemical, biophysical and structural studies identified the C-terminal Bromo Adjacent Homology (BAH) domain of TNRC18 (TNRC18BAH) as a H3K9me3-specific reader, and its N-terminal segment as a platform for direct recruitment of co-repressors such as TRIM28 and HDAC-Sin3-NCoR complexes, thereby enforcing optimal repression of the H3K9me3-demarcated ERVs. Point mutagenesis that disrupts the TNRC18BAH-mediated H3K9me3 engagement caused neonatal lethality in mice and, in multiple mammalian cell models, led to de-repressed expression of ERVs, affecting the landscape of cis-regulatory elements and thus gene-expression programs. Collectively, this study describes a previously-unknown TNRC18BAH-directed H3K9me3-sensing pathway, which operates to epigenetically silence the evolutionarily young ERVs, thereby exerting profound impacts on host genome integrity, transcriptomic regulation, immunity, and development.
2023-07-24 | GSE200834 | GEO
Project description:Trimethylation of histone H3 lysine 9 (H3K9me3) is critical for regulation of gene repression and heterochromatin formation, cell-fate determination, and organismal development. In particular, H3K9me3 provides an essential mechanism for silencing various transposon elements (TEs). However, previous studies showed that the canonical H3K9me3 readers (e.g. HP1 and MPP8) play rather limited roles in silencing endogenous retroviruses (ERVs), one of major TE classes in the mammalian genome. Here, we report that Trinucleotide Repeat Containing 18 (TNRC18), a previously under-studied chromatin regulator, recognizes H3K9me3 and directly binds ERVs, mediating ERV silencing. Our biochemical, biophysical and structural studies identified the C-terminal Bromo Adjacent Homology (BAH) domain of TNRC18 (TNRC18BAH) as a H3K9me3-specific reader, and its N-terminal segment as a platform for direct recruitment of co-repressors such as TRIM28 and HDAC-Sin3-NCoR complexes, thereby enforcing optimal repression of the H3K9me3-demarcated ERVs. Point mutagenesis that disrupts the TNRC18BAH-mediated H3K9me3 engagement caused neonatal lethality in mice and, in multiple mammalian cell models, led to de-repressed expression of ERVs, affecting the landscape of cis-regulatory elements and thus gene-expression programs. Collectively, this study describes a previously-unknown TNRC18BAH-directed H3K9me3-sensing pathway, which operates to epigenetically silence the evolutionarily young ERVs, thereby exerting profound impacts on host genome integrity, transcriptomic regulation, immunity, and development.
2023-07-24 | GSE233826 | GEO
Project description:Trimethylation of histone H3 lysine 9 (H3K9me3) is critical for regulation of gene repression and heterochromatin formation, cell-fate determination, and organismal development. In particular, H3K9me3 provides an essential mechanism for silencing various transposon elements (TEs). However, previous studies showed that the canonical H3K9me3 readers (e.g. HP1 and MPP8) play rather limited roles in silencing endogenous retroviruses (ERVs), one of major TE classes in the mammalian genome. Here, we report that Trinucleotide Repeat Containing 18 (TNRC18), a previously under-studied chromatin regulator, recognizes H3K9me3 and directly binds ERVs, mediating ERV silencing. Our biochemical, biophysical and structural studies identified the C-terminal Bromo Adjacent Homology (BAH) domain of TNRC18 (TNRC18BAH) as a H3K9me3-specific reader, and its N-terminal segment as a platform for direct recruitment of co-repressors such as TRIM28 and HDAC-Sin3-NCoR complexes, thereby enforcing optimal repression of the H3K9me3-demarcated ERVs. Point mutagenesis that disrupts the TNRC18BAH-mediated H3K9me3 engagement caused neonatal lethality in mice and, in multiple mammalian cell models, led to de-repressed expression of ERVs, affecting the landscape of cis-regulatory elements and thus gene-expression programs. Collectively, this study describes a previously-unknown TNRC18BAH-directed H3K9me3-sensing pathway, which operates to epigenetically silence the evolutionarily young ERVs, thereby exerting profound impacts on host genome integrity, transcriptomic regulation, immunity, and development.
2023-07-24 | GSE233829 | GEO
Project description:Transposable elements (TEs) are among the most dynamic parts of genomes. Since TEs are potentially deleterious, eukaryotes silence them through epigenetic mechanisms such as repressive histone modifications and DNA methylation. We previously reported that Arabidopsis TEs, called VANDALs, counteract epigenetic silencing through a group of sequence-specific anti-silencing proteins, VANCs. VANC proteins bind to noncoding regions of specific VANDAL copies and induce loss of silent chromatin marks. The VANC target regions form tandem repeats, which diverge rapidly. Sequence-specific anti-silencing allows these TEs to proliferate with minimum host damage. Here, we show that RNA-directed DNA methylation (RdDM) efficiently targets noncoding regions of VANDAL TEs to silence them de novo. Thus, escape from RdDM could be a primary event leading to the rapid evolution and diversification of sequence-specific anti-silencing systems. We propose that this selfish behavior of TEs paradoxically could make them diverse and less harmful to the host.
| S-SCDT-10_15252-EMBR_202256678 | biostudies-other
Project description:The mutagenic activity of transposable elements (TEs) is suppressed by epigenetic silencing and small interfering RNAs (siRNAs), especially in gametes that could transmit transposed elements to the next generation. In pollen from the model plant Arabidopsis, we show that TEs are unexpectedly reactivated and transpose, but only in the pollen vegetative nucleus, which accompanies the sperm cells but does not provide DNA to the fertilized zygote. TE expression coincides with downregulation of the heterochromatin remodeler decrease in DNA methylation 1 and of many TE siRNAs. However, 21 nucleotide siRNAs from Athila retrotransposons are generated and accumulate in pollen and sperm, suggesting that siRNA from TEs activated in the vegetative nucleus can target silencing in gametes. We propose a conserved role for reprogramming in germline companion cells, such as nurse cells in insects and vegetative nuclei in plants, to reveal intact TEs in the genome and regulate their activity in gametes.
| S-EPMC2661848 | biostudies-literature
Project description:RNA interference-related silencing mechanisms concern very diverse and distinct biological processes, from gene regulation (via the microRNA pathway) to defense against molecular parasites (through the small interfering RNA and the Piwi-interacting RNA pathways). Small non-coding RNAs serve as specificity factors that guide effector proteins to ribonucleic acid targets via base-pairing interactions, to achieve transcriptional or post-transcriptional regulation. Because of the small sequence complementarity required for microRNA-dependent post-transcriptional regulation, thousands of microRNA (miRNA) putative targets have been annotated in Drosophila. In Drosophila somatic ovarian cells, genomic parasites, such as transposable elements (TEs), are transcriptionally repressed by chromatin changes induced by Piwi-interacting RNAs (piRNAs) that prevent them from invading the germinal genome. Here we show, for the first time, that a functional miRNA pathway is required for the piRNA-mediated transcriptional silencing of TEs in this tissue. Global miRNA depletion, caused by tissue- and stage-specific knock down of drosha (involved in miRNA biogenesis), AGO1 or gawky (both responsible for miRNA activity), resulted in loss of TE-derived piRNAs and chromatin-mediated transcriptional de-silencing of TEs. This specific TE de-repression was also observed upon individual titration (by expression of the complementary miRNA sponge) of two miRNAs (miR-14 and miR-34) as well as in a miR-14 loss-of-function mutant background. Interestingly, the miRNA defects differentially affected TE- and 3' UTR-derived piRNAs. To our knowledge, this is the first indication of possible differences in the biogenesis or stability of TE- and 3' UTR-derived piRNAs. This work is one of the examples of detectable phenotypes caused by loss of individual miRNAs in Drosophila and the first genetic evidence that miRNAs have a role in the maintenance of genome stability via piRNA-mediated TE repression.
| S-EPMC4451950 | biostudies-literature
Project description:Transposable elements (TEs) are DNA sequences that can move within the genome. TEs have greatly shaped the genomes, transcriptomes, and proteomes of the host organisms through a variety of mechanisms. However, TEs generally disrupt genes and destabilize the host genomes, which substantially reduce fitness of the host organisms. Understanding the genomic distribution and evolutionary dynamics of TEs will greatly deepen our understanding of the TE-mediated biological processes. Most TE insertions are highly polymorphic in Drosophila melanogaster, providing us a good system to investigate the evolution of TEs at the population level. Decades of theoretical and experimental studies have well established "transposition-selection" population genetics model, which assumes that the equilibrium between TE replication and purifying selection determines the copy number of TEs in the genome. In the last decade, P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) were demonstrated to be master repressors of TE activities in Drosophila. The discovery of piRNAs revolutionized our understanding of TE repression, because it reveals that the host organisms have evolved an adaptive mechanism to defend against TE invasion. Tremendous progress has been made to understand the molecular mechanisms by which piRNAs repress active TEs, although many details in this process remain to be further explored. The interaction between piRNAs and TEs well explains the molecular mechanisms underlying hybrid dysgenesis for the I-R and P-M systems in Drosophila, which have puzzled evolutionary biologists for decades. The piRNA repression pathway provides us an unparalleled system to study the co-evolutionary process between parasites and host organisms.
| S-EPMC5487533 | biostudies-other