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Genetic Variations in Type 1 Diabetes Reconfigure the 3D Chromatin Organization of T Cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE141853 | GEO | 2020/02/11

REPOSITORIES: GEO

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Genetic Variations in Type 1 Diabetes Reconfigure the 3D Chromatin Organization of T Cells [HiChIP-seq]

Project description:Despite overwhelming evidence supporting the role of genetics in susceptibility tocomplex diseases, such as autoimmune disorders, a fundamental unresolved questionis whether large numbers of sequence variants with small effect sizes can alter thespatial genome organization. Here, we provide the first report on the reconfiguration ofthe 3D genome due to nucleotide differences associated with type 1 diabetes, anautoimmune disorder. We show that the chromatin organization at T cell identity genesis identical between diabetes-susceptible and diabetes-resistant mouse strains despitethousands of sequence polymorphisms, suggesting that these loci are epigeneticallyresilient to genetic variation. However, molecular and optical mapping of genomefolding demonstrate that diabetes risk-conferring loci coalesce into close spatialproximity in T cells of diabetes-susceptible mice, forming regulatory cliques, andresulting in aberrant gene expression. Our data uncover 3D chromatin architecture asa new dimension in understanding complex diseases

2020-02-11 | GSE141847 | GEO

Genetic Variations in Type 1 Diabetes Reconfigure the 3D Chromatin Organization of T Cells [ChIP-seq]

2020-02-11 | GSE141846 | GEO

Genetic Variations in Type 1 Diabetes Reconfigure the 3D Chromatin Organization of T Cells [ATAC-seq]

2020-02-11 | GSE141845 | GEO

Genetic Variations in Type 1 Diabetes Reconfigure the 3D Chromatin Organization of T Cells [RNA-seq]

2020-02-11 | GSE141852 | GEO

Genetic Variations in Type 1 Diabetes Reconfigure the 3D Chromatin Organization of T Cells

Project description:Genetic Variations in Type 1 Diabetes Reconfigure the 3D Chromatin Organization of T Cells

| PRJNA594953 | ENA

Genetic Variations in Type 1 Diabetes Reconfigure the 3D Chromatin Organization of T Cells [HiChIP-seq]

Project description:Genetic Variations in Type 1 Diabetes Reconfigure the 3D Chromatin Organization of T Cells [HiChIP-seq]

| PRJNA594960 | ENA

Genetic Variations in Type 1 Diabetes Reconfigure the 3D Chromatin Organization of T Cells [ChIP-seq]

Project description:Genetic Variations in Type 1 Diabetes Reconfigure the 3D Chromatin Organization of T Cells [ChIP-seq]

| PRJNA594961 | ENA

Genetic Variations in Type 1 Diabetes Reconfigure the 3D Chromatin Organization of T Cells [ATAC-seq]

Project description:Genetic Variations in Type 1 Diabetes Reconfigure the 3D Chromatin Organization of T Cells [ATAC-seq]

| PRJNA594958 | ENA

Genetic Variations in Type 1 Diabetes Reconfigure the 3D Chromatin Organization of T Cells [RNA-seq]

Project description:Genetic Variations in Type 1 Diabetes Reconfigure the 3D Chromatin Organization of T Cells [RNA-seq]

| PRJNA594959 | ENA

Genetic Variation in Type 1 Diabetes Reconfigures the 3D Chromatin Organization of T Cells and Alters Gene Expression.

Project description:Genetics is a major determinant of susceptibility to autoimmune disorders. Here, we examined whether genome organization provides resilience or susceptibility to sequence variations, and how this would contribute to the molecular etiology of an autoimmune disease. We generated high-resolution maps of linear and 3D genome organization in thymocytes of NOD mice, a model of type 1 diabetes (T1D), and the diabetes-resistant C57BL/6 mice. Multi-enhancer interactions formed at genomic regions harboring genes with prominent roles in T cell development in both strains. However, diabetes risk-conferring loci coalesced enhancers and promoters in NOD, but not C57BL/6 thymocytes. 3D genome mapping of NODxC57BL/6 F1 thymocytes revealed that genomic misfolding in NOD mice is mediated in cis. Moreover, immune cells infiltrating the pancreas of humans with T1D exhibited increased expression of genes located on misfolded loci in mice. Thus, genetic variation leads to altered 3D chromatin architecture and associated changes in gene expression that may underlie autoimmune pathology.

| S-EPMC7152927 | biostudies-literature

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