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Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription.

ABSTRACT: Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription.

PROVIDER: PRJEB4764 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR356365_1.fastq.gz	Fastqsanger.gz
	ERR356365_2.fastq.gz	Fastqsanger.gz
	ERR356366_1.fastq.gz	Fastqsanger.gz
	ERR356366_2.fastq.gz	Fastqsanger.gz
	ERR356367_1.fastq.gz	Fastqsanger.gz

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Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription.

Project description:Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription.

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Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription.

Project description:DNA sequence variation has been associated with quantitative changes in molecular phenotypes such as gene expression, but its impact on chromatin states is poorly characterized. To understand the interplay between chromatin and genetic control of gene regulation, we quantified allelic variability in transcription factor binding, histone modifications, and gene expression within humans. We found abundant allelic specificity in chromatin and extensive local, short-range, and long-range allelic coordination among the studied molecular phenotypes. We observed genetic influence on most of these phenotypes, with histone modifications exhibiting strong context-dependent behavior. Our results implicate transcription factors as primary mediators of sequence-specific regulation of gene expression programs, with histone modifications frequently reflecting the primary regulatory event.

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Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription.

Project description:ChIP-seq experiment of 14 human lymphoblastoid cell line samples from the 1000 Genomes sample set (http://www.1000genomes.org/). Dataset includes two parent-daughter trios (CEU and YRI populations) and additional eight unrelated individuals (CEU population). This accession contains raw and mapped ChIP-seq read data, other assays in this study are available under accession E-MTAB-1883 (RNA-seq, https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1883) and E-MTAB-1885 (GRO-seq, https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1885/).

2013-10-17 | E-MTAB-1884 | biostudies-arrayexpress

Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription.

Project description:Transcriptome sequencing (RNA-seq) experiment of 14 human lymphoblastoid cell line samples from the 1000 Genomes sample set (http://www.1000genomes.org/). Dataset includes two parent-daughter trios (CEU and YRI populations) and additional eight unrelated individuals (CEU population). This accession contains raw and mapped RNA-seq read data, other assays in this study are available under accession E-MTAB-1884 (ChIP-seq, https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1884) and E-MTAB-1885 (GRO-seq, https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1885).

2013-10-17 | E-MTAB-1883 | biostudies-arrayexpress

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Project description:Nascent transcriptome sequencing (GRO-seq) experiment of 3 human lymphoblastoid cell line samples from the 1000 Genomes sample set (http://www.1000genomes.org/). Dataset includes one parent-daughter trio (CEU populations). This accession contains raw, mapped, and processed GRO-seq read data, other assays in this study are available under accession E-MTAB-1884 (ChIP-seq, https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1884) and E-MTAB-1883 (RNA-seq, https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1883/).

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Methylation QTLs are associated with coordinated changes in transcription factor binding, histone modifications, and gene expression levels

Project description:This SuperSeries is composed of the SubSeries listed below. DNA methylation is an important epigenetic regulator of gene expression. Recent studies have revealed widespread associations between genetic variation and methylation levels. However, the mechanistic links between genetic variation and methylation remain unclear. To begin addressing this gap, we collected methylation data at ~300,000 loci in lymphoblastoid cell lines (LCLs) from 64 HapMap Yoruba individuals, and genome-wide bisulfite sequence data in ten of these individuals. We identified (at an FDR of 10%) 13,915 *cis* methylation QTLs (meQTLs), i.e., CpG sites in which changes in DNA methylation are associated with genetic variation at proximal loci. We found that meQTLs are frequently associated with changes in methylation at multiple CpGs across regions of up to 3 kb. Interestingly, meQTLs are also frequently associated with variation in other properties of gene regulation, including histone modifications, DNase I accessibility, chromatin accessibility, and expression levels of nearby genes. These observations suggest that genetic variants may lead to coordinated molecular changes in all of these regulatory phenotypes. One plausible driver of coordinated changes in different regulatory mechanisms is variation in transcription factor (TF) binding. Indeed, we found that SNPs that change predicted TF binding affinities are significantly enriched for associations with DNA methylation at nearby CpGs.

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Methylation QTLs are associated with coordinated changes in transcription factor binding, histone modifications, and gene expression levels [Bisulfite-array]

Project description:DNA methylation is an important epigenetic regulator of gene expression. Recent studies have revealed widespread associations between genetic variation and methylation levels. However, the mechanistic links between genetic variation and methylation remain unclear. To begin addressing this gap, we collected methylation data at ~300,000 loci in lymphoblastoid cell lines (LCLs) from 64 HapMap Yoruba individuals, and genome-wide bisulfite sequence data in ten of these individuals. We identified 11,752 methylation QTLs (meQTLs)—i.e., loci in which genetic variation is significantly associated with changes in DNA methylation. We found that meQTLs are frequently associated with changes in methylation at multiple CpGs across regions of up to 3 kb. Interestingly, meQTLs are also frequently associated with variation in other properties of gene regulation, including histone modifications, DNaseI accessibility, chromatin accessibility, and expression levels of nearby genes. These observations suggest a shared and coordinated molecular variation in all of these regulatory phenotypes. One plausible driver of coordinated changes in different regulatory mechanisms is variation in transcription factor (TF) binding. Indeed, we found that both changes in putative TF binding affinity and changes in the strength of TF binding footprints are associated with variation in DNA methylation near the TF binding sites. Considered together, our observations are consistent with a model whereby changes in TF binding may frequently drive coordinated changes in DNA methylation, histone modification, and gene expression levels. Bisulfite converted DNA from 64 individuals was hybridized to the Illumina Infinium HumanMethylation450 BeadChip

2014-05-09 | E-GEOD-57481 | biostudies-arrayexpress

Methylation QTLs are associated with coordinated changes in transcription factor binding, histone modifications, and gene expression levels [Bisulfite-array]

Project description:DNA methylation is an important epigenetic regulator of gene expression. Recent studies have revealed widespread associations between genetic variation and methylation levels. However, the mechanistic links between genetic variation and methylation remain unclear. To begin addressing this gap, we collected methylation data at ~300,000 loci in lymphoblastoid cell lines (LCLs) from 64 HapMap Yoruba individuals, and genome-wide bisulfite sequence data in ten of these individuals. We identified (at an FDR of 10%) 13,915 *cis* methylation QTLs (meQTLs), i.e., CpG sites in which changes in DNA methylation are associated with genetic variation at proximal loci. We found that meQTLs are frequently associated with changes in methylation at multiple CpGs across regions of up to 3 kb. Interestingly, meQTLs are also frequently associated with variation in other properties of gene regulation, including histone modifications, DNase I accessibility, chromatin accessibility, and expression levels of nearby genes. These observations suggest that genetic variants may lead to coordinated molecular changes in all of these regulatory phenotypes. One plausible driver of coordinated changes in different regulatory mechanisms is variation in transcription factor (TF) binding. Indeed, we found that SNPs that change predicted TF binding affinities are significantly enriched for associations with DNA methylation at nearby CpGs.

2014-05-09 | GSE57481 | GEO

Methylation QTLs are associated with coordinated changes in transcription factor binding, histone modifications, and gene expression levels [Bisulfite-Seq]

Project description:DNA methylation is an important epigenetic regulator of gene expression. Recent studies have revealed widespread associations between genetic variation and methylation levels. However, the mechanistic links between genetic variation and methylation remain unclear. To begin addressing this gap, we collected methylation data at ~300,000 loci in lymphoblastoid cell lines (LCLs) from 64 HapMap Yoruba individuals, and genome-wide bisulfite sequence data in ten of these individuals. We identified (at an FDR of 10%) 13,915 *cis* methylation QTLs (meQTLs), i.e., CpG sites in which changes in DNA methylation are associated with genetic variation at proximal loci. We found that meQTLs are frequently associated with changes in methylation at multiple CpGs across regions of up to 3 kb. Interestingly, meQTLs are also frequently associated with variation in other properties of gene regulation, including histone modifications, DNase I accessibility, chromatin accessibility, and expression levels of nearby genes. These observations suggest that genetic variants may lead to coordinated molecular changes in all of these regulatory phenotypes. One plausible driver of coordinated changes in different regulatory mechanisms is variation in transcription factor (TF) binding. Indeed, we found that SNPs that change predicted TF binding affinities are significantly enriched for associations with DNA methylation at nearby CpGs.

2014-05-09 | GSE57471 | GEO

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