MTF-1 is a crucial transcription factor involved in the cellular response to heavy-metal load and other stresses by specifically binding to metal response elements (MREs). Thus far only a handful of direct target genes are known for this transcription factor, limiting our understanding of the biological network it governs. In this article we try to employ a computational strategy based on the generation of literature-based positional weight matrices (PWM) and log-likelihood scoring of the candidate binding sites (BSs) for identification of direct targets of the transcription factor MTF-1 in human and mouse. Through comparisons, we explore the conservation and unique characteristics between two species. Our results show that the numbers of MREs differ dramatically between species and their positions relative to their cognate promoter is also flexible. Importantly, we identify a set of target genes generally well conserved between human and mouse. Finally, by combining expression analysis we provide two putative targets (HMGCR and CYP51A), which regulate lipid metabolism conserved in human and mouse. Overall, interspecies comparison from our study may provide some valuable information for further studying human Wilson disease (WD) using mouse model systems.