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

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

PROVIDER: PRJNA573934 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10180804_1.fastq.gz	Fastqsanger.gz
	SRR10180804_2.fastq.gz	Fastqsanger.gz
	SRR10180805_1.fastq.gz	Fastqsanger.gz
	SRR10180805_2.fastq.gz	Fastqsanger.gz
	SRR10180806_1.fastq.gz	Fastqsanger.gz

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

Project description:Transcriptional silencers in Drosophila serve a dual role as transcriptional enhancers in alternate cellular contexts

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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.

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

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

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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).

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Transcriptional Silencers in Drosophila Serve a Dual Role as Transcriptional Enhancers in Alternate Cellular Contexts.

Project description:A major challenge in biology is to understand how complex gene expression patterns are encoded in the genome. While transcriptional enhancers have been studied extensively, few transcriptional silencers have been identified, and they remain poorly understood. Here, we used a novel strategy to screen hundreds of sequences for tissue-specific silencer activity in whole Drosophila embryos. Almost all of the transcriptional silencers that we identified were also active enhancers in other cellular contexts. These elements are bound by more transcription factors than non-silencers. A subset of these silencers forms long-range contacts with promoters. Deletion of a silencer caused derepression of its target gene. Our results challenge the common practice of treating enhancers and silencers as separate classes of regulatory elements and suggest the possibility that thousands or more bifunctional CRMs remain to be discovered in Drosophila and 104-105 in humans.

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

Project description:This SuperSeries is composed of the SubSeries listed below.

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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.

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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.

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Polycomb Mediated Chromatin Organization Reveals Transcriptional Silencers Required for Embryonic Development

Project description:Polycomb repressive complex 2 (PRC2), a key regulator of metazoan development, induces transcriptional silencing by organizing repressive chromatin structures. To understand PRC2 associated genome topology, we performed chromatin interaction analyses focusing on three core subunits of PRC2 in embryonic stem cells (ESCs). Our comprehensive and high-resolution PRC2 interactome reveals connectivity networks manifested by the extensive looping between distal regulatory elements (DREs) and genes controlling differentiation. The deletion of these non-coding DREs in mice results in transcriptional de-repression and embryonic lethality. While functioning as silencers in ESCs, these DREs can transition into active enhancers during development, suggesting their dual regulatory activities. Integrative analysis of the three dimensional genome organization and spatial clusters of PRC2-chromatin hubs reveals the compact, peripheral assembly as the structural basis of the silencing compartments. Our study uncovers the molecular identity of PRC2 silencers, their associated genome architectures, and offers the exciting possibility of targeted re-activation of epigenetically silenced genes.

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