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Natural variation of histone modification and its impact on gene expression in rat

ABSTRACT: Natural variation of histone modification and its impact on gene expression in rat

PROVIDER: PRJEB3022 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR125683.fastq.gz	Fastqsanger.gz
	ERR125684.fastq.gz	Fastqsanger.gz
	ERR125685.fastq.gz	Fastqsanger.gz
	ERR125686.fastq.gz	Fastqsanger.gz
	ERR125687.fastq.gz	Fastqsanger.gz

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Natural variation of histone modification and its impact on gene expression in rat

Project description:Histone modifications are epigenetic marks that play fundamental roles in many biological processes including the control of chromatin-mediated regulation of gene expression. To begin to understand the impact of natural variation on histone methylation levels we generated and quantified large-scale genome-wide ChIP-seq data in a panel of rat recombinant inbred strains and their parental progenitors. Linkage analysis identified hundreds of cis- and trans-acting loci responsible for quantitative differences in histone trimethyl-lysine levels in left ventricular heart and liver tissues. We assessed the association of histone methylation and gene expression levels by generating deep RNA-seq profiles across the segregating population. Among the main findings, causal modelling of DNA variation together with histone methylation and gene expression levels enhanced the prediction of gene expression traits (eQTLs) by ~20%. Moreover, allele specific differences of histone trimethyl-lysine levels at alternative promoters were associated with differential usage of transcriptional start sites. Our data suggest that genetic variation has widespread impact on histone modifications. The highly adapted interplay between DNA variation and chromatin structure has consequences on gene and isoform expression as direct functional outcome and demonstrated new avenues to find novel genotype Ð phenotype relationships. NOTE: Additional processed data files were added to this experiment on the 24th April 2014. They are in the zip archive E-MTAB-1102.additional.1.zip which is available under the 'Click to browse all available files' link.

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Project description:Histone modifications are epigenetic marks that play fundamental roles in many biological processes including the control of chromatin-mediated regulation of gene expression. Little is known about interindividual variability of histone modification levels across the genome and to what extent they are influenced by genetic variation. We annotated the rat genome with histone modification maps, identified differences in histone trimethyl-lysine levels among strains, and described their underlying genetic basis at the genome-wide scale using ChIP-seq in heart and liver tissues in a panel of rat recombinant inbred and their progenitor strains. We identified extensive variation of histone methylation levels among individuals and mapped hundreds of underlying cis- and trans-acting loci throughout the genome that regulate histone methylation levels in an allele-specific manner. Interestingly, most histone methylation level variation was trans-linked and the most prominent QTL identified influenced H3K4me3 levels at 899 putative promoters throughout the genome in the heart. Cis- acting variation was enriched in binding sites of distinct transcription factors in heart and liver. The integrated analysis of DNA variation together with histone methylation and gene expression levels showed that histoneQTLs are an important predictor of gene expression and that a joint analysis significantly enhanced the prediction of gene expression traits (eQTLs). Our data suggest that genetic variation has a widespread impact on histone trimethylation marks that may help to uncover novel genotype-phenotype relationships.

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