Cell https://doi.org/10.1016/j.cell.2018.04.018 (2018)

How pioneer transcription factors (TFs) bind in a cell type–specific manner has remained unclear. In Cell, Glass and colleagues evaluate the effect of single-nucleotide polymorphisms and of insertions or deletions on TF binding and gene expression in bone marrow–derived macrophages from five inbred mouse strains. They find that expression of 10% of all transcripts varies by at least fourfold across the five strains. TF binding is affected more by genetic variation than by active histone modifications, nascent RNA production or mature RNA transcripts. Strain-specific differences result mainly from variation in distal cis-regulatory elements. The majority of strain-specific TF binding correlates with variation in binding sites for a network of TFs located nearby, but some is due to regional interactions between cis-regulatory elements, independently of local genetic variation.