AUTHOR=Luo Wen , Ren Xueyi , Chen Jiahui , Li Limin , Lu Shiyi , Chen Tian , Nie Qinghua , Zhang Xiquan 

TITLE=TP63 Transcripts Play Opposite Roles in Chicken Skeletal Muscle Differentiation

JOURNAL=Frontiers in Physiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.01298

DOI=10.3389/fphys.2018.01298

ISSN=1664-042X

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