To combat DNA damage, organisms mount a DNA damage response (DDR) that results in cell cycle regulation, DNA repair and, in severe cases, cell death. Underscoring the importance of gene regulation in this response, studies in Arabidopsis have demonstrated that all of the aforementioned processes rely on SUPPRESSOR OF GAMMA RESPONSE 1 (SOG1), a NAC family transcription factor (TF) that has been functionally equated to the mammalian tumor suppressor, p53. However, the expression networks connecting SOG1 to these processes remain largely unknown and, although the DDR spans from minutes to hours, most transcriptomic data correspond to single time-point snapshots. Here, we generated transcriptional models of the DDR from GAMMA (γ)-irradiated wild-type and sog1 seedlings during a 24-hour time course using DREM, the Dynamic Regulatory Events Miner, revealing 11 coexpressed gene groups with distinct biological functions and cis-regulatory features. Within these networks, additional chromatin immunoprecipitation and transcriptomic experiments revealed that SOG1 is the major activator, directly targeting the most strongly up-regulated genes, including TFs, repair factors, and early cell cycle regulators, while three MYB3R TFs are the major repressors, specifically targeting the most strongly down-regulated genes, which mainly correspond to G2/M cell cycle-regulated genes. Together these models reveal the temporal dynamics of the transcriptional events triggered by γ-irradiation and connects these events to TFs and biological processes over a time scale commensurate with key processes coordinated in response to DNA damage, greatly expanding our understanding of the DDR.
The homeoprotein DLX3 and tumor suppressor p53 co-regulate cell cycle progression and squamous tumor growth
