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 |
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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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