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Systematic identification of silencers in human cells

ABSTRACT: Systematic identification of silencers in human cells

PROVIDER: PRJNA427579 | ENA |

REPOSITORIES: ENA

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Systematic identification of silencers in human cells

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

Systematic identification of silencers in human cells.

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smRNAs generated by single-stranded and double-stranded silencers

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

Information Content Differentiates Enhancers From Silencers in Mouse Photoreceptors

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

Systematic Interrogation of Human Promoters

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Transcriptional silencers in Drosophila serve a dual role as transcriptional enhancers in alternate cellular contexts [HiChIP]

Project description:Silencers active in the Drosophila embryonic mesoderm were identified by reporter assays in dissociated embryonic cells. We find that, despite the presence of ChIP peaks for known transcriptional corepressors and marks of repressed chromatin, the only significantly enriched source of mesodermal silencers is non-mesodermal enhancers. We present evidence that a subset of silencers acts by looping to target promoters.

2019-09-25 | GSE137949 | GEO

Systematic Identification of Factors Crucial for Provirus Silencing in Embryonic Stem Cells

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Transcriptional silencers in Drosophila serve a dual role as transcriptional enhancers in alternate cellular contexts [Hi-C]

Project description:We generated HiC data from sorted mesodermal and non-mesodermal cells from stage 11-12 Drosophila embryos to explore the distribution of genomic contacts of silencers and non-silencers (identified elsewhere in the manuscript).

2019-09-25 | GSE137955 | GEO

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