Document Type
Article
Publication Date
4-16-2021
Identifier
DOI: 10.1038/s41467-021-22548-8
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.
Journal Title
Nat Commun
Volume
12
Issue
1
First Page
2298
Last Page
2298
Recommended Citation
Watt S, Vasquez L, Walter K, et al. Genetic perturbation of PU.1 binding and chromatin looping at neutrophil enhancers associates with autoimmune disease. Nat Commun. 2021;12(1):2298. Published 2021 Apr 16. doi:10.1038/s41467-021-22548-8
Comments
Grant support
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Publisher's Link: https://www.nature.com/articles/s41467-021-22548-8