Office of Biological and Environmental Research
DOE Lowdose Radiation Program Workshop V
Abstract
Title: Using Co-Regulation to Understand Low-Dose Ionizing Radiation Responsive Genes and Pathways.
Authors: Matthew A. Coleman, Xiaowen Xin, Terence James Critchlow, Ivan Ovcharenko, Francesco Marchetti, and krish Krishnan and Andrew J. Wyrobek.
Institutions: BioSciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550. Contact information coleman16@llnl.gov.
Our objective of this project is to utilize genome-scale expression microarray data in conjunction with DNA sequence/pattern databases to identify and validate gene regulatory elements that may control and differentiate aspects of cellular responses to low dose IR. We hypothesize that: a) low dose responsive genes share arrangements of short regulatory sequences (elements and modules), b) the specific components of the low dose regulatory modules vary with the shape of the dose response for that gene and the ability of the cells to undergo a radioadaptive response, and c) low dose regulatory modules contribute to low dose genetic susceptibility and radiation sensitivity. To address these hypotheses we will identify regulatory elements and modules that are specific for low dose responsive genes. These regulatory sequences will provide a sequence-based understanding of how cells respond to IR. The regulatory elements can then be used to predict additional low dose responsive gene networks that can be subsequently tested for validation and genetic variation. We will also investigate the function and regulatory association for promoter modules that we previously identified as being regulated by TP53 in response to IR. Together these IR regulatory elements should prove useful for risk assessment through understanding their contribution to both genetic susceptibility and IR sensitivity.
This work is performed under the auspices of the U.S. Department of Energy by the University of California, Lawrence Livermore National Laboratory under Contract No. W-7405-Eng-48 with funding from the Biological and Environmental Research (BER), DOE Low Dose Radiation Research Program, grant KP110202.
