Genetic perturbation of PU.1 binding and chromatin looping at neutrophil enhancers associates with autoimmune disease.
Nat Commun
; 12(1): 2298, 2021 04 16.
Article
em En
| MEDLINE
| ID: mdl-33863903
ABSTRACT
Neutrophils play fundamental roles in innate immune response, shape adaptive immunity, and are a potentially causal cell type underpinning genetic associations with immune system traits and diseases. Here, we profile the binding of myeloid master regulator PU.1 in primary neutrophils across nearly a hundred volunteers. We show that variants associated with differential PU.1 binding underlie genetically-driven differences in cell count and susceptibility to autoimmune and inflammatory diseases. We integrate these results with other multi-individual genomic readouts, revealing coordinated effects of PU.1 binding variants on the local chromatin state, enhancer-promoter contacts and downstream gene expression, and providing a functional interpretation for 27 genes underlying immune traits. Collectively, these results demonstrate the functional role of PU.1 and its target enhancers in neutrophil transcriptional control and immune disease susceptibility.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Autoimunes
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Transativadores
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Regulação da Expressão Gênica
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Proteínas Proto-Oncogênicas
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Elementos Facilitadores Genéticos
/
Neutrófilos
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2021
Tipo de documento:
Article