Dataset Information

Candidate silencer elements for the human and mouse genomes.

ABSTRACT: The study of gene regulation is dominated by a focus on the control of gene activation or increase in the level of expression. Just as critical is the process of gene repression or silencing. Chromatin signatures have identified enhancers, however, genome-wide identification of silencers by computational or experimental approaches are lacking. Here, we first define uncharacterized cis-regulatory elements likely containing silencers and find that 41.5% of ~7500 tested elements show silencer activity using massively parallel reporter assay (MPRA). We trained a support vector machine classifier based on MPRA data to predict candidate silencers in over 100 human and mouse cell or tissue types. The predicted candidate silencers exhibit characteristics expected of silencers. Leveraging promoter-capture HiC data, we find that over 50% of silencers are interacting with gene promoters having very low to no expression. Our results suggest a general strategy for genome-wide identification and characterization of silencer elements.

SUBMITTER: Doni Jayavelu N

PROVIDER: S-EPMC7044160 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Candidate silencer elements for the human and mouse genomes.

Doni Jayavelu Naresh N Jajodia Ajay A Mishra Arpit A Hawkins R David RD

Nature communications 20200226 1

The study of gene regulation is dominated by a focus on the control of gene activation or increase in the level of expression. Just as critical is the process of gene repression or silencing. Chromatin signatures have identified enhancers, however, genome-wide identification of silencers by computational or experimental approaches are lacking. Here, we first define uncharacterized cis-regulatory elements likely containing silencers and find that 41.5% of ~7500 tested elements show silencer activ ...[more]

PMID: 32103011

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Project description:Subtelomeric chromatin is subject to evolutionarily conserved complex epigenetic regulation and is implicated in numerous aspects of cellular function including formation of heterochromatin, regulation of different stress response pathways, and control of lifespan. Subtelomeric DNA is characterized by the presence of specific repeated segments that serve to propagate silencing activities or to protect chromosomal regions from spreading epigenetic control. Using condition-specific genome wide chromatin immunoprecipitation and expression data, we show that several yeast transcription factors regulate subtelomeric silencing in response to various environmental stimuli through conditional association with proto-silencing regions called X elements. In this context, some factors control the propagation of silencing toward centromeres in response to stimuli affecting stress responses and metabolism, whereas others appear to influence boundaries of silencing, regulating telomere-proximal genes in Y’ elements. The factors implicated here have previously been shown to control adjacent genes at intrachromosomal positions, suggesting dual functionality of the factors and a possible mechanism of coordinating intrachromosomal gene expression with subtelomeric silencing. These data suggest a fundamental mechanism to coordinate telomere biology related to aging and adaptation with cellular environment and the activities of other cellular processes. These are Chip-CHIP data for myc tagged Oaf1p transcription factor from S. cerevisiae grown in the presence or absence of the fatty acid oleate. ChIP-CHIP analysis was performed to determine the genomic distribution of Oaf1p transcription factor in the BY4742 yeast strain after growth in 0.1% glucose, or in the presence of the fatty acid oleate. Three biological replicates for each growth condition (in the presence of low glucose or 5 h after a shift to medium containing oleate as a carbon source). ChIP samples were amplified by PCR, labelled and hybridized to 50-mer tiling arrays covering both strands of the entire yeast genome at a 64 bp resolution.

Dataset Information

Candidate silencer elements for the human and mouse genomes.

Publications

Candidate silencer elements for the human and mouse genomes.

Similar Datasets

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