SOG1 activator and MYB3R repressors regulate a complex DNA damage network in .

Proc Natl Acad Sci U S A

Plant Molecular and Cellular Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037;

Published: December 2018

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 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 seedlings during a 24-hour time course using DREM, the Dynamic Regulatory Events Miner, revealing 11 coexpressed gene groups with distinct biological functions and -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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310815PMC
http://dx.doi.org/10.1073/pnas.1810582115DOI Listing

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