@article{22f44972c6914bd1b78510ceb937bf59,
title = "In vivo RNA-seq and ChIP-seq analyses show an obligatory role for the C terminus of p53 in conferring tissue-specific radiation sensitivity",
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 sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) analyses of radiation-treated mouse organs identifies both shared and tissue-specific p53 transcriptional responses. As expected, the p53 targets shared among thymus and spleen are enriched in apoptotic targets. 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 that an additional role of the C terminus is 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.",
keywords = "CP: Cancer, CP: Molecular biology, ChIP-sequencing, RNA-sequencing, apoptosis, gene expression, p53, radiosensitivity, tissue specificity",
author = "Lois Resnick-Silverman and Royce Zhou and Campbell, {Moray J.} and Ian Leibling and Ramon Parsons and Manfredi, {James J.}",
note = "Funding Information: The preparation of libraries and subsequent sequencing for the RNA-seq analyses was performed at the Epigenomics Core of Weill Cornell Medicine. The sequencing of the libraries for ChIP-seq analyses was performed at the Department of Oncological Sciences Sequencing Core Facility at the Icahn School of Medicine at Mount Sinai. The services of both Cores are gratefully acknowledged. The advice of Vincent Anguiano, Songhee Back, Carol Prives, and Ramy Rahme is gratefully acknowledged. This work was supported by grants from the National Cancer Institute to J.J.M. ( R01 CA257548 ) and to R.P. ( R35 CA220491 ). Funding Information: The preparation of libraries and subsequent sequencing for the RNA-seq analyses was performed at the Epigenomics Core of Weill Cornell Medicine. The sequencing of the libraries for ChIP-seq analyses was performed at the Department of Oncological Sciences Sequencing Core Facility at the Icahn School of Medicine at Mount Sinai. The services of both Cores are gratefully acknowledged. The advice of Vincent Anguiano, Songhee Back, Carol Prives, and Ramy Rahme is gratefully acknowledged. This work was supported by grants from the National Cancer Institute to J.J.M. (R01 CA257548) and to R.P. (R35 CA220491). The study was conceived by L.R.-S. and J.J.M. Experiments were designed by L.R.-S. R.Z. I.L. and J.J.M. Experiments were conducted and analyzed by L.R.-S. R.Z. M.J.C. R.P. and J.J.M. The manuscript was prepared by L.R.-S. and J.J.M. with help from the other authors. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. Publisher Copyright: {\textcopyright} 2023 The Author(s)",
year = "2023",
month = mar,
day = "28",
doi = "10.1016/j.celrep.2023.112216",
language = "English",
volume = "42",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "3",
}