Dataset Information

The cis-Regulatory Atlas of the Mouse Immune System.

ABSTRACT: A complete chart of cis-regulatory elements and their dynamic activity is necessary to understand the transcriptional basis of differentiation and function of an organ system. We generated matched epigenome and transcriptome measurements in 86 primary cell types that span the mouse immune system and its differentiation cascades. This breadth of data enable variance components analysis that suggests that genes fall into two distinct classes, controlled by either enhancer- or promoter-driven logic, and multiple regression that connects genes to the enhancers that regulate them. Relating transcription factor (TF) expression to the genome-wide accessibility of their binding motifs classifies them as predominantly openers or closers of local chromatin accessibility, pinpointing specific cis-regulatory elements where binding of given TFs is likely functionally relevant, validated by chromatin immunoprecipitation sequencing (ChIP-seq). Overall, this cis-regulatory atlas provides a trove of information on transcriptional regulation through immune differentiation and a foundational scaffold to define key regulatory events throughout the immunological genome.

SUBMITTER: Yoshida H

PROVIDER: S-EPMC6785993 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Publications

The cis-Regulatory Atlas of the Mouse Immune System.

Yoshida Hideyuki H Lareau Caleb A CA Ramirez Ricardo N RN Rose Samuel A SA Maier Barbara B Wroblewska Aleksandra A Desland Fiona F Chudnovskiy Aleksey A Mortha Arthur A Dominguez Claudia C Tellier Julie J Kim Edy E Dwyer Dan D Shinton Susan S Nabekura Tsukasa T Qi YiLin Y Yu Bingfei B Robinette Michelle M Kim Ki-Wook KW Wagers Amy A Rhoads Andrew A Nutt Stephen L SL Brown Brian D BD Mostafavi Sara S Buenrostro Jason D JD Benoist Christophe C

Cell 20190124 4

A complete chart of cis-regulatory elements and their dynamic activity is necessary to understand the transcriptional basis of differentiation and function of an organ system. We generated matched epigenome and transcriptome measurements in 86 primary cell types that span the mouse immune system and its differentiation cascades. This breadth of data enable variance components analysis that suggests that genes fall into two distinct classes, controlled by either enhancer- or promoter-driven logic ...[more]

PMID: 30686579

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Project description:BackgroundChanges in gene expression are known to be responsible for phenotypic variation and susceptibility to diseases. Identification and annotation of the genomic sequence variants that cause gene expression changes is therefore likely to lead to a better understanding of the cause of disease at the molecular level. In this study we investigate the pattern of single nucleotide polymorphisms (SNPs) in genes for which the mRNA levels show cis-genetic linkage (gene expression quantitative trait loci mapping in cis, or cis-eQTLs) in segregating mouse populations. Such genes are expected to have polymorphisms near their physical location (cis-variations) that affect their mRNA levels by altering one or more of the cis-regulatory elements. This led us to characterize the SNPs in promoter (5 Kb upstream) and non-coding gene regions (introns and 5 Kb downstream) (cis-SNPs) and the effects they may have on putative transcription factor binding sites.ResultsWe demonstrate that the cis-eQTL genes (CEGs) have a significantly higher frequency of cis-SNPs compared to non-CEGs (when both sets are taken from the non-IBD regions, i.e. regions not identical by descent). Most CEGs having cis-SNPs do not contain these SNPs in the phylogenetically conserved regions. In those CEGs that contain cis-SNPs in the phylogenetically conserved regions, enrichment of cis-SNPs occurs both within and outside of the conserved sequences. A higher fraction of CEGs are also seen to harbor cis-SNP that affect predicted transcription factor binding sites, a likely consequence of the higher cis-SNPs density in these genes.ConclusionThis present study provides the first genome-wide investigation of the putative cis-regulatory variations in a large set of genes whose levels of expression give rise to cis-linkage in segregating mammalian populations. Our results provide insights into the challenges that exist in identifying polymorphisms regulating gene expression using bioinformatic sequence analysis approaches. The data provided herein should benefit future investigations in this area.

Dataset Information

The cis-Regulatory Atlas of the Mouse Immune System.

Publications

The cis-Regulatory Atlas of the Mouse Immune System.

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