Transcriptional and epigenetic regulation following ionizing radiation exposure in a skin model system
EMSL Project ID
40691
Abstract
Dynamic post-translational modifications (PTMs) occurring on histones play essential roles in regulating transcription of specific target genes and in the epigenetic reprogramming occurring during disease and following exposure to various environmental insults. A number of histone PTMs including acetylation and methylation are generally linked to activation and repression of transcription, however, both the localization and effects of specific histone isoforms on gene expression are likely to be promoter and gene specific. Therefore, sequencing of the DNA associated with specific histone PTMs will provide valuable information on which genes are activated under specific physiological conditions. Moreover, histone PTMs can direct epigenetic programming by themselves or work in concert with DNA methylation for long-term suppression of specific genes during differentiation and disease. In this proposal, we plan to utilize EMSL's next generation sequencing capabilities created through ARRA funding to characterize global and targeted transcriptional responses following exposure to ionizing radiation. We will first generate global transcriptomic data that will be combined with parallel proteomic and metabolomic data to generate a comprehensive biosignature of a human skin tissue equivalent exposed to multiple doses of ionizing radiation. We will then perform more targeted studies to identify gene expression patterns and DNA sequences associated with known histone modifications involved in transcriptional and epigenetic regulation using chromatin immunoprecipitation sequencing (ChIP-seq). Finally, we will perform ChIP seq on novel radiation sensitive histone isoforms identified through a complimentary EMSL intact protein analysis platform and user proposal to determine the genes and DNA sequences associated with specific histone isoforms. Merging of the ChIP-Seq capability with complimentary proteomic approaches will provide EMSL with a very unique capability to comprehensively study transcriptional and epigenetic regulation at the protein and DNA level. This proposal will directly benefit ongoing work funded by the DOE low dose radiation research program and the Defense Threat Reduction Agency as well as provide necessary data to obtain additional funding from NIH and other agencies.
Project Details
Project type
Exploratory Research
Start Date
2010-09-29
End Date
2011-10-03
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Hengel S, JT Aldrich, KM Waters, L Pasa-Tolic, and DL Stenoien. 2014. "Quantitative Proteomic Profiling of Low Dose Ionizing Radiation Effects in a Human Skin Model." Proteomes 2(3):382-398. doi:10.3390/proteomes2030382
Tilton S.C., L.M. Markillie, S. Hays, R.C. Taylor, and D.L. Stenoien. 2016. "Identification of differential gene expression patterns after acute exposure to high and low doses of low-LET ionizing radiation in a reconstituted human skin tissue." Radiation Research 186, no. 5:531-538. PNNL-SA-116819. doi:10.1667/RR14471.1