TP63 Transcripts Play Opposite Roles in Chicken Skeletal Muscle Differentiation.

ABSTRACT: Tumor protein 63 (TP63) comprises multiple isoforms and plays an important role during embryonic development. It has been shown that TP63 knockdown inhibits myogenic differentiation, but which isoform is involved in the underlying myogenic regulation remains uncertain. Here, we found that two transcripts of TP63, namely, TAp63? and ?Np63?, are expressed in chicken skeletal muscle. These two transcripts have distinct expression patterns and opposite functions in skeletal muscle development. TAp63 has higher expression in skeletal muscle than in other tissues, and its expression is gradually upregulated during chicken primary myoblast differentiation. ?Np63 can be expressed in multiple tissues and exhibits stable expression during myoblast differentiation. TAp63? overexpression inhibits myoblast proliferation, induces cell cycle arrest, and enhances myoblast differentiation. However, although ?Np63? has no significant effect on cell proliferation, the overexpression of ?Np63? inhibits myoblast differentiation. Using isoform-specific overexpression assays following RNA-sequencing, we identified potential downstream genes of TAp63? and ?Np63? in myoblast. Bioinformatics analyses and experimental verification results showed that the differentially expressed genes (DEGs) between the TAp63? and control groups were enriched in the cell cycle pathway, whereas the DEGs between the ?Np63? and control groups were enriched in muscle system process, muscle contraction, and myopathy. These findings provide new insights into the function and expression of TP63 during skeletal muscle development, and indicate that one gene may play two opposite roles during a single cellular process.

SUBMITTER: Luo W 

PROVIDER: S-EPMC6157316 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature