SmRNAs generated by single-stranded and double-stranded silencers
Ontology highlight
ABSTRACT:
ORGANISM(S): Arabidopsis thaliana
PROVIDER: GSE39398 | GEO | 2013/12/23
SECONDARY ACCESSION(S): PRJNA170936
REPOSITORIES: GEO
Similar Datasets
Project description:To investigate possible smRNAs linked to TMM silencing by single-stranded and double-stranded silencers, we determined sequences of smRNAs by the Illumina high-throughput sequencing platform and compared silencing efficiency of different strategies. We found that single-stranded silencer alone could promote the production of smRNAs. smRNA profiles of 2-week-old wide type seedlings (WT) and different silencers were generated by Illumina Genome Analyzer IIx.
2013-12-23 | E-GEOD-39398 | biostudies-arrayexpress
Project description:The majority of the human genome does not encode proteins. Many of these noncoding regions contain important regulatory sequences that control gene expression. To date, most studies have focused on activators such as enhancers, but regions that repress gene expression⎯silencers⎯have not been systematically studied. We have developed a system that identifies silencer regions in a genome-wide fashion based on silencer-mediated transcriptional repression of caspase 9. We found that silencers are widely distributed and may function in a tissue-specific fashion. These silencers harbor unique epigenetic signatures and are associated with specific transcription factors. Silencers also act at multiple genes, and at the level of chromosomal domains and long-range interactions. Deletion of silencer regions linked to the drug transporter genes ABCC2 and ABCG2 caused chemo-resistance. Overall, our study demonstrates that tissue-specific silencing is widespread throughout the human genome and likely contributes significantly to the regulation of gene expression and human biology.
2020-01-09 | GSE108536 | GEO
Project description:smRNAs generated by single-stranded and double-stranded silencers
| PRJNA170936 | ENA
Project description:Enhancers and silencers often depend on the same transcription factors (TFs) and are imperfectly distinguished from each other by genomic assays of TF binding or chromatin state. To identify sequence features that define enhancers and silencers, we assayed massively parallel reporter libraries of genomic sequences targeted by the photoreceptor TF CRX and found instances of enhancer, silencer, or no activity. Both enhancers and silencers contain more TF motifs than inactive sequences, but enhancers contain motifs from a more diverse collection of TFs. We developed a measure of information content that describes the number and diversity of motifs in a sequence and found that, while both enhancers and silencers depend on CRX motifs, enhancers have higher information content. Our results indicate that enhancers contain motifs for a diverse but degenerate collection of TFs, while silencers depend on a smaller and less diverse collection of TFs.
2021-01-30 | GSE165812 | GEO
Project description:Both upregulation and downregulation by cis-regulatory elements help establish precise gene expression. Our understanding of how elements repress transcriptional activity is far more limited than activating elements. To address this gap, we characterized RE1, a group of transcriptional silencers bound by REST, on a genome-wide scale using an optimized massively parallel reporter assay (MPRAduo). MPRAduo empirically defined a minimal binding strength of REST required by silencer (REST m-value), above which multiple cofactors colocalize and act to directly silence transcription. We identified 1,500 human variants that alter RE1 silencing and found their effect sizes are predictable when they overlap with REST binding sites above the m-value. In addition, we demonstrate that non-canonical REST binding motifs exhibit silencer function only if they precisely align two half sites with specific spacer length. Our results show mechanistic insights into RE1 silencer which allows us to predict its activity and effect of variants on RE1, providing a paradigm for performing genome-wide functional characterization transcription factors binding sites.
2022-02-17 | GSE196171 | GEO
Project description:Both upregulation and downregulation by cis-regulatory elements help establish precise gene expression. Our understanding of how elements repress transcriptional activity is far more limited than activating elements. To address this gap, we characterized RE1, a group of transcriptional silencers bound by REST, on a genome-wide scale using an optimized massively parallel reporter assay (MPRAduo). MPRAduo empirically defined a minimal binding strength of REST required by silencer (REST m-value), above which multiple cofactors colocalize and act to directly silence transcription. We identified 1,500 human variants that alter RE1 silencing and found their effect sizes are predictable when they overlap with REST binding sites above the m-value. In addition, we demonstrate that non-canonical REST binding motifs exhibit silencer function only if they precisely align two half sites with specific spacer length. Our results show mechanistic insights into RE1 silencer which allows us to predict its activity and effect of variants on RE1, providing a paradigm for performing genome-wide functional characterization transcription factors binding sites.
2022-09-30 | GSE212253 | GEO
Project description:Human silencers have been shown to exist and regulate developmental gene expression. However, the functional importance of human silencers need to be elucidated such as the working mode and whether they can form “super-silencers”. Here, through interrogating two putative silencer components of FGF18 gene, we found that two silencers can cooperate via compensated chromatin interactions to form the “super-silencer”. Furthermore, double knock-out of two silencers exhibited synergistic upregulation of FGF18 expression and changes of cell identity. To disturb the “super-silencers”, we applied the combinational treatment of GSK343 and X5050 (“GR”). We found that GR led to severe loss of TADs and loops, while any single treatment only had mild changes. Such changes of TADs and loops may due to the decreased CTCF proteins upon the GR treatment. Moreover, GSK343 and X5050 can work synergistically to upregulated the super-silencer controlled apoptotic genes, thus gave rise to antitumor effects including apoptosis, cell cycle arrest and tumor growth inhibition. Overall, our data demonstrated the first example of “super-silencer” and showed that combinational usage of GSK343 and X5050 maybe the potential drug to curing cancers through disruption of “super-silencers”.
2024-05-08 | GSE193484 | GEO
Project description:Human silencers have been shown to exist and regulate developmental gene expression. However, the functional importance of human silencers need to be elucidated such as the working mode and whether they can form “super-silencers”. Here, through interrogating two putative silencer components of FGF18 gene, we found that two silencers can cooperate via compensated chromatin interactions to form the “super-silencer”. Furthermore, double knock-out of two silencers exhibited synergistic upregulation of FGF18 expression and changes of cell identity. To disturb the “super-silencers”, we applied the combinational treatment of GSK343 and X5050 (“GR”). We found that GR led to severe loss of TADs and loops, while any single treatment only had mild changes. Such changes of TADs and loops may due to the decreased CTCF proteins upon the GR treatment. Moreover, GSK343 and X5050 can work synergistically to upregulated the super-silencer controlled apoptotic genes, thus gave rise to antitumor effects including apoptosis, cell cycle arrest and tumor growth inhibition. Overall, our data demonstrated the first example of “super-silencer” and showed that combinational usage of GSK343 and X5050 maybe the potential drug to curing cancers through disruption of “super-silencers”.
2024-05-08 | GSE193483 | GEO
Project description:Human silencers have been shown to exist and regulate developmental gene expression. However, the functional importance of human silencers need to be elucidated such as the working mode and whether they can form “super-silencers”. Here, through interrogating two putative silencer components of FGF18 gene, we found that two silencers can cooperate via compensated chromatin interactions to form the “super-silencer”. Furthermore, double knock-out of two silencers exhibited synergistic upregulation of FGF18 expression and changes of cell identity. To disturb the “super-silencers”, we applied the combinational treatment of GSK343 and X5050 (“GR”). We found that GR led to severe loss of TADs and loops, while any single treatment only had mild changes. Such changes of TADs and loops may due to the decreased CTCF proteins upon the GR treatment. Moreover, GSK343 and X5050 can work synergistically to upregulated the super-silencer controlled apoptotic genes, thus gave rise to antitumor effects including apoptosis, cell cycle arrest and tumor growth inhibition. Overall, our data demonstrated the first example of “super-silencer” and showed that combinational usage of GSK343 and X5050 maybe the potential drug to curing cancers through disruption of “super-silencers”.
2024-05-08 | GSE193481 | GEO
Project description:Human silencers have been shown to exist and regulate developmental gene expression. However, the functional importance of human silencers need to be elucidated such as the working mode and whether they can form “super-silencers”. Here, through interrogating two putative silencer components of FGF18 gene, we found that two silencers can cooperate via compensated chromatin interactions to form the “super-silencer”. Furthermore, double knock-out of two silencers exhibited synergistic upregulation of FGF18 expression and changes of cell identity. To disturb the “super-silencers”, we applied the combinational treatment of GSK343 and X5050 (“GR”). We found that GR led to severe loss of TADs and loops, while any single treatment only had mild changes. Such changes of TADs and loops may due to the decreased CTCF proteins upon the GR treatment. Moreover, GSK343 and X5050 can work synergistically to upregulated the super-silencer controlled apoptotic genes, thus gave rise to antitumor effects including apoptosis, cell cycle arrest and tumor growth inhibition. Overall, our data demonstrated the first example of “super-silencer” and showed that combinational usage of GSK343 and X5050 maybe the potential drug to curing cancers through disruption of “super-silencers”.
2024-05-08 | GSE193486 | GEO