Characterization of chicken p53 transcriptional function via parallel genome- wide chromatin occupancy and gene expression analysis

The tumor suppressor p53, which acts primarily as a transcription factor, can regulate infec-tions from various viruses in chickens. However, the underlying mechanisms of the antiviral functions of chicken p53 (chp53) remain unclear due to the lack of detailed information on its transcriptional regulation. Here, to gain comprehensive insights into chp53 tran-scriptional regulatory function in a global and unbiased manner, we determined the genome-wide chromatin occupancy of chp53 by chromatin immunoprecipitation, which was followed by sequencing and chp53-mediated gene expression profile by RNA sequencing using chemi-cally immortalized leghorn male hepatoma (LMH) cells with ectopic expression of chp53 as the model. The integrated parallel genome-wide chromatin occupancy and gene expression analysis characterized chp53 chro-matin occupancy and identified 754 direct target genes of chp53. Furthermore, functional annotation and cross -species comparative biological analyses revealed the con-served key biological functions and DNA binding motifs of p53 between chickens and humans, which may be due to the consensus amino acid sequence and structure of p53 DNA-binding domains. The present study, to our knowledge, provides the first comprehensive characteri-zation of the chp53 transcriptional regulatory network, and can possibly help to improve our understanding of p53 transcriptional regulatory mechanisms and their antiviral functions in chickens.

Automated summary

In this study, the chp53 transcriptional regulatory network was comprehensively characterized through analysis of chromatin occupancy and gene expression, providing insights into the underlying mechanisms of chp53's antiviral functions in chickens. The findings also contribute to a better understanding of p53 transcriptional regulatory mechanisms.