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A microRNA expression and regulatory element activity atlas of the mouse immune system.

ABSTRACT: To better define the control of immune system regulation, we generated an atlas of microRNA (miRNA) expression from 63 mouse immune cell populations and connected these signatures with assay for transposase-accessible chromatin using sequencing (ATAC-seq), chromatin immunoprecipitation followed by sequencing (ChIP-seq) and nascent RNA profiles to establish a map of miRNA promoter and enhancer usage in immune cells. miRNA complexity was relatively low, with >90% of the miRNA compartment of each population comprising <75 miRNAs; however, each cell type had a unique miRNA signature. Integration of miRNA expression with chromatin accessibility revealed putative regulatory elements for differentially expressed miRNAs, including miR-21a, miR-146a and miR-223. The integrated maps suggest that many miRNAs utilize multiple promoters to reach high abundance and identified dominant and divergent miRNA regulatory elements between lineages and during development that may be used by clustered miRNAs, such as miR-99a/let-7c/miR-125b, to achieve distinct expression. These studies, with web-accessible data, help delineate the cis-regulatory elements controlling miRNA signatures of the immune system.

SUBMITTER: Rose SA

PROVIDER: S-EPMC8480231 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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A microRNA expression and regulatory element activity atlas of the mouse immune system.

Rose Samuel A SA Wroblewska Aleksandra A Dhainaut Maxime M Yoshida Hideyuki H Shaffer Jonathan M JM Bektesevic Anela A Ben-Zvi Benjamin B Rhoads Andrew A Kim Edy Y EY Yu Bingfei B Lavin Yonit Y Merad Miriam M Buenrostro Jason D JD Brown Brian D BD

Nature immunology 20210607 7

To better define the control of immune system regulation, we generated an atlas of microRNA (miRNA) expression from 63 mouse immune cell populations and connected these signatures with assay for transposase-accessible chromatin using sequencing (ATAC-seq), chromatin immunoprecipitation followed by sequencing (ChIP-seq) and nascent RNA profiles to establish a map of miRNA promoter and enhancer usage in immune cells. miRNA complexity was relatively low, with >90% of the miRNA compartment of each p ...[more]

PMID: 34099919

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Project description:Regulation of microRNA (miRNA) expression contributes to a wide range of target gene expression and phenotypes. The miRNA expression in the liver, the central metabolic organ, was examined in 209 pigs, and integrated with haematological and clinical biomarkers of metabolic and overall health, mRNA-target expression levels and single-nucleotide polymorphism (SNP) genotypes. The expression levels of 426 miRNA species correlated with plasma haematological or biochemical traits (r² = |0.19-0.45|, false discovery rate < 5%). Pairs of these miRNAs and their predicted target mRNAs showing expressing levels associated with the identical traits were examined to understand how immune and metabolic traits are affected by miRNA-mediated regulatory networks derived by mapping miRNA abundance as an expression quantitative trait. In total, 221 miRNA-expression-QTL correspond to 164 SNPs and 108 miRNAs, including miR-34a, miR-30e, miR-148-3p, miR-204, miR-181-5p, miR-143-5p and let-7 g that also correlate with the biomarkers. Sixty-one SNPs were simultaneously associated with 29 miRNA and 41 mRNA species. The expression levels of 13 out of 29 miRNA were correlated with one of the biochemical or haematological traits. For example, the expression levels of miR-34a were correlated with serum phosphorus and cholesterin levels; miR-204, miR-15a and miR-16b were correlated with triglyceride. For haematological traits, the expression levels of miR-652 and miR-204 were correlated with the mean corpuscular haemoglobin concentration, and the expression of miR-143 was correlated with plateletcrit. Pleiotropic association analyses revealed genetic links between mRNA and miRNA on SSC6 for miR-34a, SSC9 for miR-708 and SSC14 for miR-652. Our analysis of miRNA and mRNA transcript profiles, their correlation with clinically important plasma parameters of hepatic functions as well as information on their genetic regulation provide novel regulatory networks and potential new biomarkers for immune and metabolic traits.

Dataset Information

A microRNA expression and regulatory element activity atlas of the mouse immune system.

Publications

A microRNA expression and regulatory element activity atlas of the mouse immune system.

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