Chromatin accessibility and gene expression during adipocyte differentiation identify context-dependent effects at cardiometabolic GWAS loci

Autor: Hannah J Perrin, Swarooparani Vadlamudi, Kevin W Currin, Karen L. Mohlke, Gautam Kumar Pandey, Markku Laakso, Michael I. Love, Kenneth K Ng, Martin Wabitsch
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Epigenomics
Cancer Research
Gene Expression
Genome-wide association study
Allelic Imbalance
Regulatory Sequences
Nucleic Acid
QH426-470
0302 clinical medicine
Animal Cells
Adipocytes
Medicine and Health Sciences
Promoter Regions
Genetic
Genetics (clinical)
Connective Tissue Cells
Genetics
Regulation of gene expression
0303 health sciences
Chromosome Biology
Cell Differentiation
Genomics
Chromatin
Adipose Tissue
Genetic Techniques
Cardiovascular Diseases
Connective Tissue
Chromatin Immunoprecipitation Sequencing
Epigenetics
Anatomy
Cellular Types
Research Article
Quantitative Trait Loci
Locus (genetics)
Context (language use)
Biology
03 medical and health sciences
Metabolic Diseases
Genome-Wide Association Studies
Adipocyte Differentiation
Humans
Gene Regulation
Molecular Biology
Gene
Ecology
Evolution
Behavior and Systematics
Alleles
030304 developmental biology
Binding Sites
Biology and Life Sciences
Computational Biology
Human Genetics
Cell Biology
Genome Analysis
Biological Tissue
Genetic Loci
Expression quantitative trait loci
030217 neurology & neurosurgery
Genome-Wide Association Study
Developmental Biology
Zdroj: PLoS Genetics, Vol 17, Iss 10, p e1009865 (2021)
PLoS Genetics
PLoS Genetics, Vol 17, Iss 10 (2021)
ISSN: 1553-7404
1553-7390
Popis: Chromatin accessibility and gene expression in relevant cell contexts can guide identification of regulatory elements and mechanisms at genome-wide association study (GWAS) loci. To identify regulatory elements that display differential activity across adipocyte differentiation, we performed ATAC-seq and RNA-seq in a human cell model of preadipocytes and adipocytes at days 4 and 14 of differentiation. For comparison, we created a consensus map of ATAC-seq peaks in 11 human subcutaneous adipose tissue samples. We identified 58,387 context-dependent chromatin accessibility peaks and 3,090 context-dependent genes between all timepoint comparisons (log2 fold change>1, FDR
Author summary Cardiovascular and metabolic diseases are widespread, and an increased understanding of genetic mechanisms behind these diseases could improve treatment. Chromatin accessibility and gene expression in relevant cell contexts can guide identification of regulatory elements and genetic mechanisms for disease traits. A relevant context for cardiovascular and metabolic disease traits is adipocyte differentiation. To identify regulatory elements and genes that display differences in activity during adipocyte differentiation, we profiled chromatin accessibility and gene expression in a human cell model of preadipocytes and adipocytes. We identified chromatin regions that change accessibility during differentiation and predicted genes they may affect. We also linked these chromatin regions to genetic variants associated with risk of disease. At one genomic region linked to fatty acids, a chromatin region more accessible in adipocytes linked to a fatty acid synthesis gene and exhibited allelic differences in transcriptional activity in adipocytes but not preadipocytes. These results demonstrate that chromatin regions and genes that change during cell context can guide discovery of regulatory variants and aid identification of disease mechanisms.
Databáze: OpenAIRE
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