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Promoter sequence and architecture determine expression variability and confer robustness to genetic variants [GM12878]

ABSTRACT: Promoter sequence and architecture determine expression variability and confer robustness to genetic variants [GM12878]

PROVIDER: PRJNA777788 | ENA |

REPOSITORIES: ENA

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Promoter sequence and architecture determine expression variability and confer robustness to genetic variants

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Promoter sequence and architecture determine expression variability and confer robustness to genetic variants [GM12878]

Project description:Genetic and environmental exposures cause variability in gene expression. Although most genes are affected in a population, their effect sizes vary greatly, indicating the existence of regulatory mechanisms that could amplify or attenuate expression variability. Here, we investigate the relationship between the sequence and transcription start site architectures of promoters and their expression variability across human individuals. We find that expression variability can be largely explained by a promoter’s DNA sequence and its binding sites for specific transcription factors. We show that promoter expression variability reflects the biological process of a gene, demonstrating a selective trade-off between stability for metabolic genes and plasticity for responsive genes and those involved in signaling. Promoters with a rigid transcription start site architecture are more prone to have variable expression and to be associated with genetic variants with large effect sizes, while a flexible usage of transcription start sites within a promoter attenuates expression variability and limits genotypic effects. Our work provides insights into the variable nature of responsive genes and reveals a novel mechanism for supplying transcriptional and mutational robustness to essential genes through multiple transcription start site regions within a promoter.

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Promoter sequence and architecture determine expression variability and confer robustness to genetic variants [immortalized lymphoblastoid cell lines]

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Promoter sequence and architecture determine expression variability and confer robustness to genetic variants

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

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Homo sapiens isolate:GM12878

Project description:GM12878 MultiOmics

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Promoter capture GM12878 CD34

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Genome-wide mapping of RNA Pol II binding site (GM12878)

Project description:We report the results of chromatin immunoprecipitation following by high-thoughput sequencing (ChIP-Seq) using the GA II platform from Illumina for the human RNA Polymerase II in GM12878 cells. We have also generated a sequenced input DNA datasets for GM12878 cells. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf Map binding sites of RNA Polymerase II in the genome of GM12878 cells. The GM12878 input data has been deposited in GEO as GSM487430.

2009-12-31 | E-GEOD-19550 | biostudies-arrayexpress

Genome-wide mapping of RNA Pol III binding site (GM12878)

Project description:We report the results of chromatin immunoprecipitation following by high-thoughput sequencing (ChIP-Seq) using the GA II platform from Illumina for the human RNA Polymerase III in GM12878 cells. We have also generated a sequenced input DNA datasets for GM12878 cells. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf Map binding sites of RNA Polymerase III in the genome of GM12878 cells.

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