In humans, the zinc (Zn)-activated transcription factors (TFs) metal response element-binding transcription factor 1 (MTF-1) and ZNF658 regulate gene expression by binding to their associated DNA motifs, the metal regulatory element (MRE) and the zinc transcriptional regulatory element (ZTRE), respectively, upon activation by cellular Zn. Genome-wide bioinformatic analyses were performed to better understand how these motifs may affect TF binding. The effects of the number of MREs and their distance from transcriptional start sites (TSSs) were examined in a secondary analysis of gene expression. MTF-1 is also predicted to form complex regulatory networks with miRNAs via the MRE in the promoters of miRNAs and their target genes. ZNF658 may be responsible for a global Zn deficiency response by binding selectively to ZTRE permutations that occur closer to transcriptional start sites (ex: ZTRE-E) versus others (ex: ZTRE-A) under varied Zn concentrations.
