Variation in PU.1 binding and chromatin looping at neutrophil enhancers influences autoimmune disease susceptibility
Alice L. Mann,
Posted 29 Apr 2019
bioRxiv DOI: 10.1101/620260
Posted 29 Apr 2019
Neutrophils play fundamental roles in innate inflammatory response, shape adaptive immunity, and have been identified as a potentially causal cell type underpinning genetic associations with immune system traits and diseases. The majority of these variants are non-coding and the underlying mechanisms are not fully understood. Here, we profiled the binding of one of the principal myeloid transcriptional regulators, PU.1, in primary neutrophils across nearly a hundred volunteers, and elucidate the coordinated genetic effects of PU.1 binding variation, local chromatin state, promoter-enhancer interactions and gene expression. We show that PU.1 binding and the associated chain of molecular changes underlie genetically-driven differences in cell count and autoimmune disease susceptibility. Our results advance interpretation for genetic loci associated with neutrophil biology and immune disease.
- Downloaded 663 times
- Download rankings, all-time:
- Site-wide: 23,573 out of 100,334
- In genetics: 1,450 out of 4,997
- Year to date:
- Site-wide: 27,620 out of 100,334
- Since beginning of last month:
- Site-wide: None out of 100,334
Downloads over time
Distribution of downloads per paper, site-wide
- 20 Oct 2020: Support for sorting preprints using Twitter activity has been removed, at least temporarily, until a new source of social media activity data becomes available.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!