西亚试剂：Effect of natural genetic variation on enhancer selection a

Effect of natural genetic variation on enhancer selection and function

S. Heinz，C. E. Romanoski，C. Benner，K. A. Allison，M. U. Kaikkonen，L. D. Orozco& C. K. Glass

The mechanisms by which genetic variation affects transcription regulation and s at the nucleotide level are incompletely understood. Here we use natural genetic variation as an in vivo mutagenesis screen to assess the genome-wide effects of sequence variation on lineage-determining and signal-specific transcription factor binding， epigenomics and transcriptional outcomes in primary macrophages from different mouse strains. We find substantial genetic evidence to support the concept that lineage-determining transcription factors define epigenetic and transcriptomic states by selecting enhancer-like regions in the genome in a collaborative fashion and facilitating binding of signal-dependent factors. This hierarchical model of transcription factor function suggests that limited sets of genomic data for lineage-determining transcription factors and informative histone modifications can be used for the prioritization of disease-associated regulatory variants.

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