Genome-wide analysis of p53 transcriptional programs in B cells upon exposure to genotoxic stress in vivo

• DOI: 10.18632/oncotarget.5232
• Publication Date: 2015-09-28T16:51:29Z
• Authors: Claudia Tonelli; Marco J. Morelli; Salvatore Bianchi; Luca Rotta; Thelma Capra; Arianna Sabò; Stefano Campaner; Bruno Amati
• Keywords: Chromatin immunoprecipitation; Transcription

// Claudia Tonelli 1 , Marco J. Morelli 2 Salvatore Bianchi Luca Rotta Thelma Capra Arianna Sabò Stefano Campaner and Bruno Amati 1,2 Department of Experimental Oncology, European Institute Oncology (IEO), Milan, Italy Center for Genomic Science IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), Correspondence to: Amati, email: Keywords : p53, transcription, DNA damage, B cells, chromatin Received July 28, 2015 Accepted August 13, Published September 05, Abstract The tumor suppressor p53 is a transcription factor that coordinates the cellular response to damage. Here we provide an integrated analysis genomic occupancy p53-dependent gene regulation in splenic non-B cell compartments mice exposed whole-body ionizing radiation, providing insight into general principles activity vivo . In unstressed conditions, bound few targets; induction by radiation increased number sites, leading highly overlapping profiles different types. Comparison these with features cells revealed that, upon activation, localized at active promoters, distal enhancers, smaller set unmarked regions. At recognition canonical motif as well binding strength were associated transcriptional but not repression, indicating latter was most likely indirect. p53-activated targets constituted core type-independent response, superimposed onto type-specific program. Core genes included known p53-regulated genes, many new ones. Our data represent unique characterization vivo.