Comparison of PU.1 genomic binding across immune cells reveals cell type-specific roles in autoimmune disease
Lewis, D. A.; Shook, M. S.; Lawson, L. P.; Parameswaran, S.; Chen, X.; Edsall, L. E.; Donmez, O. A.; Yin, C.; Rosado-Tristani, D. A.; VonHandorf, A.; Dexheimer, P. J.; Forney, C. R.; Felton, J. M.; Diouf, A. A.; Dunn, K. A.; Smith, D. F.; Rothenberg, M. E.; Seidman, J. S.; Troutman, T. D.; Glass, C. K.; Waggoner, S. N.; Weirauch, M. T.; Kottyan, L. C.
Show abstract
Transcription factors play key roles in cellular biology. Their genomic binding events are enriched at disease- and trait-associated genetic risk loci in particular cellular contexts. To examine this phenomenon in depth, we constructed a PU.1 (SPI1) binding atlas by uniformly processing 260 PU.1 ChIP-seq datasets spanning many immune cell types. Comparison of ChIP-seq peaks across eight major immune cell types identifies shared and cell type-specific PU.1 binding events. DNA sequence analyses reveals context-specific binding shaped by both canonical PU.1 motifs and motifs from partner transcription factor families. Integration of this atlas with genome-wide association studies of blood cell traits and immune-mediated diseases reveals strong enrichment for PU.1 binding events at genetic risk loci and extensive genotype-dependent PU.1 genomic occupancy. We identify cellular contexts in which PU.1 enrichment is most pronounced, including at autoimmune disease loci within EBV-positive B cells. Together, these results define cellular, infectious, and genetic contexts of PU.1 binding that help connect noncoding variation to human phenotypes.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Functional Inference of Gene Regulation using Single-Cell Multi-Omics 97%
- Gene regulatory network inference from CRISPR perturbations in primary CD4+ T cells elucidates the genomic basis of immune disease 97%
- Colocalization of blood cell traits GWAS associations and variation in PU.1 genomic occupancy prioritizes causal noncoding regulatory variants 96%
Similar papers in this journal
- Genome-wide discovery of lupus genetic risk variant allelic regulatory activity 97%
- Shared and distinct molecular effects of regulatory genetic variants provide insight into mechanisms of distal enhancer-promoter communication 96%
- Genome-scale spatial mapping of the Hodgkin lymphoma microenvironment identifies tumor cell survival factors 96%
Similar papers in this journal
- Prioritization of autoimmune disease-associated genetic variants that perturb regulatory element activity in T cells 98%
- Linking candidate causal autoimmune variants to T cell networks using genetic and epigenetic screens in primary human T cells. 97%
- ArchR: An integrative and scalable software package for single-cell chromatin accessibility analysis 95%
Similar papers in this journal
- Chromatin conformation dynamics during CD4+ T cell activation implicates autoimmune disease-associated genes and regulatory elements 98%
- Chromatin accessibility variation provides insights into missing regulation underlying immune-mediated diseases 96%
- Foxp3 depends on Ikaros for control of regulatory T cell gene expression and function 96%
Similar papers in this journal
- Remodeling of Il4-Il13-Il5 locus underlies selective gene expression 95%
- Mapping pQTLs of circulating inflammatory proteins identifies drivers of immune-related disease risk and novel therapeutic targets 95%
- High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.