المؤلفون: Ivy Aneas, Donna C. Decker, Chanie L. Howard, Débora R. Sobreira, Noboru J. Sakabe, Kelly M. Blaine, Michelle M. Stein, Cara L. Hrusch, Lindsey E. Montefiori, Juan Tena, Kevin M. Magnaye, Selene M. Clay, James E. Gern, Daniel J. Jackson, Matthew C. Altman, Edward T. Naureckas, Douglas K. Hogarth, Steven R. White, Jose Luis Gomez-Skarmeta, Nathan Schoetler, Carole Ober, Anne I. Sperling, Marcelo A. Nóbrega

المصدر: Nature Communications, Vol 12, Iss 1, Pp 1-12 (2021)

مصطلحات موضوعية: Science

الوصف: Susceptibility to asthma and severity of symptoms are regulated by a number of different genomic regions. Here the authors characterise a 5kb regulatory region and demonstrate genetic and topological regulation of IL33 and association with disease in different human cohorts.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/91de69f13ca849d4bde27470e200f0b0Test

المؤلفون: Amelia C. Joslin, Débora R. Sobreira, Grace T. Hansen, Noboru J. Sakabe, Ivy Aneas, Lindsey E. Montefiori, Kathryn M. Farris, Jing Gu, Donna M. Lehman, Carole Ober, Xin He, Marcelo A. Nóbrega

المصدر: Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021)

مصطلحات موضوعية: Science

الوصف: Many genetic loci have been linked to obesity, but knowledge of their functional mechanisms is limited. Here, the authors perform reporter assays and temporal functional genomics data generation to characterize obesity genetic loci and find that loci often harbor multiple functional variants.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/fb7e892c9745454a8d337ec16d1a90bbTest

المؤلفون: Steven R. White, Juan J. Tena, James E. Gern, Débora R. Sobreira, Chanie L. Howard, Kevin M. Magnaye, Carole Ober, Kelly M. Blaine, José Luis Gómez-Skarmeta, Noboru J. Sakabe, Cara L. Hrusch, Anne I. Sperling, Michelle M. Stein, Marcelo A. Nobrega, Edward T. Naureckas, Donna C. Decker, Ivy Aneas, Nathan Schoetler, Lindsey E. Montefiori, Daniel J. Jackson, Douglas K. Hogarth, Matthew C. Altman, Selene M. Clay

المساهمون: National Institutes of Health (US)

المصدر: Nature Communications
Nature Communications, Vol 12, Iss 1, Pp 1-12 (2021)
Digital.CSIC. Repositorio Institucional del CSIC
instname

مصطلحات موضوعية: Male, Science, General Physics and Astronomy, Mice, Transgenic, Locus (genetics), Single-nucleotide polymorphism, Genome-wide association study, Biology, Genome-wide association studies, Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, Chromosome conformation capture, Gene expression, Animals, Humans, Genetic Predisposition to Disease, Allele, Promoter Regions, Genetic, Enhancer, Alleles, Zebrafish, Genetic association, Genetics, Multidisciplinary, Interleukins, General Chemistry, Interleukin-33, Asthma, Chromatin, Gene regulation, Enhancer Elements, Genetic, Female, Octamer Transcription Factor-1

الوصف: Genome-wide association studies (GWAS) have implicated the IL33 locus in asthma, but the underlying mechanisms remain unclear. Here, we identify a 5 kb region within the GWAS-defined segment that acts as an enhancer-blocking element in vivo and in vitro. Chromatin conformation capture showed that this 5 kb region loops to the IL33 promoter, potentially regulating its expression. We show that the asthma-associated single nucleotide polymorphism (SNP) rs1888909, located within the 5 kb region, is associated with IL33 gene expression in human airway epithelial cells and IL-33 protein expression in human plasma, potentially through differential binding of OCT-1 (POU2F1) to the asthma-risk allele. Our data demonstrate that asthma-associated variants at the IL33 locus mediate allele-specific regulatory activity and IL33 expression, providing a mechanism through which a regulatory SNP contributes to genetic risk of asthma.
This work was supported by NIH grants R01 HL118758, R01 HL128075, R01 HL119577, R01 HL085197, U19 AI095230, UG3 OD023282 and UM1 AI114271.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::675806710a5bb89f7c09fc586438962cTest
https://doi.org/10.1038/s41467-021-26347-zTest

المؤلفون: Noboru J. Sakabe, Ivy Aneas, Xin He, Carole Ober, Lindsey E. Montefiori, Amelia C Joslin, Jing Gu, Donna M. Lehman, Débora R. Sobreira, Marcelo A. Nobrega, Grace T Hansen, Kathryn M. Farris

المصدر: Nature Communications
Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021)

مصطلحات موضوعية: Epigenomics, Heart Defects, Congenital, Science, Quantitative Trait Loci, Hypothalamus, General Physics and Astronomy, Genome-wide association study, Computational biology, MAP Kinase Kinase 5, Biology, Quantitative trait locus, Polymorphism, Single Nucleotide, Article, Gigantism, General Biochemistry, Genetics and Molecular Biology, Sarcoplasmic Reticulum Calcium-Transporting ATPases, Pleiotropy, Intellectual Disability, Adipocytes, Genetic Pleiotropy, Humans, Obesity, Enhancer, Gene, Genetic association, Neurons, Multidisciplinary, Functional genomics, Arrhythmias, Cardiac, Genetic Diseases, X-Linked, General Chemistry, Gene regulation, Enhancer Elements, Genetic, Transcriptome, Protein Kinases, Genome-Wide Association Study, Transcription Factors

الوصف: Genome-wide association studies (GWAS) have identified many disease-associated variants, yet mechanisms underlying these associations remain unclear. To understand obesity-associated variants, we generate gene regulatory annotations in adipocytes and hypothalamic neurons across cellular differentiation stages. We then test variants in 97 obesity-associated loci using a massively parallel reporter assay and identify putatively causal variants that display cell type specific or cross-tissue enhancer-modulating properties. Integrating these variants with gene regulatory information suggests genes that underlie obesity GWAS associations. We also investigate a complex genomic interval on 16p11.2 where two independent loci exhibit megabase-range, cross-locus chromatin interactions. We demonstrate that variants within these two loci regulate a shared gene set. Together, our data support a model where GWAS loci contain variants that alter enhancer activity across tissues, potentially with temporally restricted effects, to impact the expression of multiple genes. This complex model has broad implications for ongoing efforts to understand GWAS.
Many genetic loci have been linked to obesity, but knowledge of their functional mechanisms is limited. Here, the authors perform reporter assays and temporal functional genomics data generation to characterize obesity genetic loci and find that loci often harbor multiple functional variants.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3a38d28748fd50ff9893c210f86b5e26Test
https://doi.org/10.1038/s41467-021-25614-3Test