Divergence of the PIERCE1 expression between mice and humans as a p53 target gene

PIERCE1, p53 induced expression 1 in Rb null cells, is a novel p53 target involved in the DNA damage response and cell cycle in mice. These facts prompted us to study the function of PIERCE1 with respect to p53-associated pathophysiology of cancer in humans. Unexpectedly, PIERCE1 did not respond to overexpression and activation of p53 in humans. In this study, we swapped p53 protein expression in human and mouse cells to find the clue of this difference between species. Human p53 expression in mouse cells upregulatedPIERCE1expression, suggesting that p53-responsive elements on thePIERCE1promoter are crucial, but not the p53 protein itself. Indeed,in silicoanalyses ofPIERCE1promoters revealed that p53-responsive elements identified in mice are not conserved in humans. Consistently, chromatin immunoprecipitation-sequencing (ChIP-seq) analyses confirmed p53 enrichment against thePIERCE1promoter region in mice, not in human cells. To complement the p53 study in mice, further promoter analyses suggested that the humanPIERCE1promoter is more similar to guinea pigs, lemurs, and dogs than to rodents. Taken together, our results confirm the differential responsiveness ofPIERCE1expression to p53 due to species differences inPIERCE1promoters. The results also show partial dissimilarity after p53 induction between mice and humans.