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The C-terminus of p53 Confers Liver-Specific Gene Regulation and Radio-Resistance in vivo [ChIP-seq]

ABSTRACT: Thymus and spleen, in contrast to liver, are radiosensitive tissues in which p53-dependent apoptosis is triggered after whole body radiation in vivo. Combined RNA-seq and ChIP-seq analyses of radiation-treated mouse organs identifies both shared and tissue-specific p53 transcriptional responses. As expected, the p53 targets shared amongst thymus and spleen are enriched in apoptotic targets. Surprisingly, the inability to upregulate these genes in the liver is not due to reduced gene occupancy. Use of an engineered mouse model shows that deletion of the C-terminus of p53 can confer radiation-induced expression of p53 apoptotic targets in the liver with concomitant increased cell death. Global RNA-seq analysis reveals an additional role of the C-terminus being also needed for transcriptional activation of liver-specific p53 targets. It is hypothesized that both suppression of apoptotic gene expression combined with enhanced activation of liver-specific targets confers tissue-specific radio-resistance.

ORGANISM(S): Mus musculus

PROVIDER: GSE203643 | GEO | 2022/06/30

REPOSITORIES: GEO

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