According to research recently published in Genome Medicine, a complex of transcription factors which includes p53, NF-kappa-B and STAT3 is responsible for regulation of miRNA-21 expression. This microRNA is significantly upregulated in stressed heart muscle and has previously been suggested as a therapeutic target in a mouse model of heart failure.
Roger Foo and colleagues used chromatin immunoprecipitation assays and high-throughput sequencing to examine transcription factor binding at the miRNA-21 locus. They found that p53 acts as a cofactor, forming a protein complex with NF-kappa-B (RELA), and that STAT3 is also required for the complex to associate with the cis-element controlling mir-21 expression. This may be a more general mechanism of control in other genes whose promoters lack a p53 consensus sequence.
The authors suggest that understanding the interactions of DNA binding proteins and regulatory elements in miRNA-21 expression will further inform future drug design.