Journal
NATURE GENETICS
Volume 50, Issue 3, Pages 424-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41588-018-0046-7
Keywords
-
Categories
Funding
- Wellcome Trust [WT098051, WT099754/Z/12/Z, WT098503]
- Estonian Research Council [MOBJD67]
- Medical Research Council [WT098503]
- MRC [MC_PC_12026] Funding Source: UKRI
Ask authors/readers for more resources
Regulatory variants are often context specific, modulating gene expression in a subset of possible cellular states. Although these genetic effects can play important roles in disease, the molecular mechanisms underlying context specificity are poorly understood. Here, we identified shared quantitative trait loci (QTLs) for chromatin accessibility and gene expression in human macrophages exposed to IFN gamma, Salmonella and IFN gamma plus Salmonella. We observed that similar to 60% of stimulus-specific expression QTLs with a detectable effect on chromatin altered the chromatin accessibility in naive cells, thus suggesting that they perturb enhancer priming. Such variants probably influence binding of cell-type-specific transcription factors, such as PU.1, which can then indirectly alter the binding of stimulus-specific transcription factors, such as NF-kappa B or STAT2. Thus, although chromatin accessibility assays are powerful for fine-mapping causal regulatory variants, detecting their downstream effects on gene expression will be challenging, requiring profiling of large numbers of stimulated cellular states and time points.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available