Similar Datasets
Project description:Long terminal repeats (LTRs), which comprise promoter and enhancer region of intact endogenous retroviruses (ERVs), are known to be co-opted for fine-tuning host-coding gene expression as cis-regulatory elements. Since LTRs are mainly silenced by the deposition of repressive epigenetic marks, a substantial activation of LTRs have been found in human cells after treatment with epigenetic inhibitors. Although LTR12C family had highest relative abundance of transcripts among the de-repressed ERV families, functional consequences of the activated LTR12C for host-coding genes remain uncover due to genome-wide alteration of epigenetic landscape resulting in broad transcriptional changes after the epigenetic inhibitor treatments. Here, we transactivated more than 600 LTR12C elements by using single guide RNA-based dCas9-Suntag-VP64, which is a kind of the site-specific targeting technology CRISPR activation system, with minimal off-target events. Interestingly, most of transactivated LTR12C elements acquired H3K27ac-marked enhancer feature, while 20% of them along with enrichment of H3K4me3-marked promoter feature. The enrichment of H3K4me3 signal was likely brought about by downstream regions of LTR12C, such as internal regions of intact ERV9 or other type of retrotransposons.
2024-08-16 | GSE243548 | GEO
Project description:Long terminal repeats (LTRs), which comprise promoter and enhancer region of intact endogenous retroviruses (ERVs), are known to be co-opted for fine-tuning host-coding gene expression as cis-regulatory elements. Since LTRs are mainly silenced by the deposition of repressive epigenetic marks, a substantial activation of LTRs have been found in human cells after treatment with epigenetic inhibitors. Although LTR12C family had highest relative abundance of transcripts among the de-repressed ERV families, functional consequences of the activated LTR12C for host-coding genes remain uncover due to genome-wide alteration of epigenetic landscape resulting in broad transcriptional changes after the epigenetic inhibitor treatments. Here, we transactivated more than 600 LTR12C elements by using single guide RNA-based dCas9-Suntag-VP64, which is a kind of the site-specific targeting technology CRISPR activation system, with minimal off-target events. Interestingly, most of transactivated LTR12C elements acquired H3K27ac-marked enhancer feature, while 20% of them along with enrichment of H3K4me3-marked promoter feature. The enrichment of H3K4me3 signal was likely brought about by downstream regions of LTR12C, such as internal regions of intact ERV9 or other type of retrotransposons.
2024-08-16 | GSE243547 | GEO
Project description:Long terminal repeats (LTRs), which comprise promoter and enhancer region of intact endogenous retroviruses (ERVs), are known to be co-opted for fine-tuning host-coding gene expression as cis-regulatory elements. Since LTRs are mainly silenced by the deposition of repressive epigenetic marks, a substantial activation of LTRs have been found in human cells after treatment with epigenetic inhibitors. Although LTR12C family had highest relative abundance of transcripts among the de-repressed ERV families, functional consequences of the activated LTR12C for host-coding genes remain uncover due to genome-wide alteration of epigenetic landscape resulting in broad transcriptional changes after the epigenetic inhibitor treatments. Here, we transactivated more than 600 LTR12C elements by using single guide RNA-based dCas9-Suntag-VP64, which is a kind of the site-specific targeting technology CRISPR activation system, with minimal off-target events. Interestingly, most of transactivated LTR12C elements acquired H3K27ac-marked enhancer feature, while 20% of them along with enrichment of H3K4me3-marked promoter feature. The enrichment of H3K4me3 signal was likely brought about by downstream regions of LTR12C, such as internal regions of intact ERV9 or other type of retrotransposons.
2024-08-16 | GSE243546 | GEO
Project description:Endogenous retrovirus LTR12C hold potential locus-dependent activities as promoter and/or enhancer
| PRJNA1018902 | ENA
Project description:Endogenous retrovirus LTR12C hold potential locus-dependent activities as promoter and/or enhancer [BiSulfite-seq]
| PRJNA1018907 | ENA
Project description:Endogenous retrovirus LTR12C hold potential locus-dependent activities as promoter and/or enhancer [RNA-seq]
| PRJNA1018900 | ENA
Project description:Endogenous retrovirus LTR12C hold potential locus-dependent activities as promoter and/or enhancer [ChIP-seq]
| PRJNA1018904 | ENA
Project description:Mus dunni endogenous virus (MDEV) is an apparently intact retrovirus that normally lies transcriptionally silent in cultured M. dunni cells, but the provirus can be activated by treatment of the cells with hydrocortisone or 5-iodo-2'-deoxyuridine. Sequence analysis of a molecular clone of the replicating virus revealed a simple retrovirus with a chimeric VL30/GALV-like structure. Interestingly, in the region of the long terminal repeat (LTR) that typically contains the retroviral transcription enhancers, we found over six 80-bp repeats with only a single mismatch, indicating that acquisition of the repeats was a recent event. Here we provide evidence for the following model of MDEV activation and replication. The MDEV provirus in M. dunni cells has a chimeric structure similar to that of the molecular clone but has only 1.15 copies of the 80-bp repeat sequence found in the molecular clone. Activating chemicals directly stimulate transcription from the LTR, allowing a low level of virus replication. Copying errors made during reverse transcription allow multimerization of the 80-bp enhancer region, resulting in viruses with higher transcriptional rates and improved fitness, but increased enhancer copy number is likely balanced by the natural instability of retroviral repeats and constraints imposed by virion packaging limits. The resultant population of replicating MDEV is widely heterogeneous, having from 2.15 to 13.15 enhancer repeats in the LTR. These results reveal a novel mechanism for regulation of transcription and replication of an endogenous retrovirus, in terms of both activation of the virus by the steroid hydrocortisone and the large number and variation in enhancer repeats observed.
| S-EPMC113028 | biostudies-literature
Project description:BackgroundHuman endogenous retroviruses (HERVs) are surviving traces of ancient retrovirus infections and now reside within the human DNA. Recently HERV expression has been detected in both normal tissues and diseased patients. However, the activities (expression levels) of individual HERV sequences are mostly unknown.ResultsWe introduce a generative mixture model, based on Hidden Markov Models, for estimating the activities of the individual HERV sequences from EST (expressed sequence tag) databases. We use the model to estimate the relative activities of 181 HERVs. We also empirically justify a faster heuristic method for HERV activity estimation and use it to estimate the activities of 2450 HERVs. The majority of the HERV activities were previously unknown.Conclusion(i) Our methods estimate activity accurately based on experiments on simulated data. (ii) Our estimate on real data shows that 7% of the HERVs are active. The active ones are spread unevenly into HERV groups and relatively uniformly in terms of estimated age. HERVs with the retroviral env gene are more often active than HERVs without env. Few of the active HERVs have open reading frames for retroviral proteins.
| S-EPMC1892069 | biostudies-literature
Project description:The functional organization of eukaryotic genomes correlates with specific patterns of histone methylations. Regulatory regions in genomes like enhancers and promoters differ in their extent of methylation of histone H3 at lysine-4 (H3K4), but it is largely unknown how the different methylation states are specified and controlled. Here, we show that the Kdm5c/Jarid1c/SMCX member of the Kdm5 family of H3K4 demethylases can be recruited to both enhancer and promoter elements in embryonic stem cells and neuronal progenitor cells via gene-specific transcription factors. Knockdown of Kdm5c deregulates transcription via local increases in H3K4me3. Our data show that restricting H3K4me3 modification at core promoters dampens transcription, but Kdm5c is required at enhancers for their full activity. Remarkably, an impaired enhancer function activates the intrinsic promoter activity of Kdm5c-bound distal elements. Our results demonstrate that the Kdm5c demethylase plays a crucial and dynamic role in the functional discrimination between enhancers and core promoters. RNA from four independent cultures from each sh Kdm5c #1, sh Kdm5c #2 and non-targeting shRNA polyclonal cell lines were hybridized in dye-swap against a common reference of RNA from IB10 ES cells.
2013-04-05 | E-GEOD-38862 | biostudies-arrayexpress