Troponin T3 associates with DNA consensus sequence that overlaps with p53 binding motifs

We recently reported that in addition to its classical cytoplasmic location, the fast skeletal muscle Troponin T3 (TnT3) shuttles to the nucleus, where it appears to perform nonclassical transcription regulatory functions. Importantly, changes in the composition of the nucleus-localized pool of TnT3 and its fragments contribute to age-dependent muscle damage and wasting. Here, using ChIP-Seq, we demonstrate that TnT3 associates with DNA consensus sequences including the TGCCT motif, which is required for p53 binding to the promoter area of p53-related genes. Gene set enrichment analysis further demonstrated that the p53 pathway was the most significantly enriched pathway among genes annotated to the TnT3 ChIP-Seq peaks. We further demonstrated a strong correlation (r = 0.78, P = 1 × 10−4) between the expression levels of TNNT3 and TP53-inducible ribonucleotide reductase regulatory subunit M2B (RRM2B) in skeletal muscle tissue of 21 lean non-diabetic human subjects and a significant (P