Common variants in signaling transcription-factor-binding sites drive phenotypic variability in red blood cell traits.

ABSTRACT: Genome-wide association studies identify genomic variants associated with human traits and diseases. Most trait-associated variants are located within cell-type-specific enhancers, but the molecular mechanisms governing phenotypic variation are less well understood. Here, we show that many enhancer variants associated with red blood cell (RBC) traits map to enhancers that are co-bound by lineage-specific master transcription factors (MTFs) and signaling transcription factors (STFs) responsive to extracellular signals. The majority of enhancer variants reside on STF and not MTF motifs, perturbing DNA binding by various STFs (BMP/TGF-β-directed SMADs or WNT-induced TCFs) and affecting target gene expression. Analyses of engineered human blood cells and expression quantitative trait loci veri

SUBMITTER: Choudhuri A 

PROVIDER: S-EPMC7876911 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature