LncRNA regulation of environmental response

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DESCRIPTION (provided by applicant): Long noncoding RNAs (lncRNAs) have emerged as a pervasive and important class of regulators of gene expression and chromatin states. We discovered that numerous lncRNAs are induced by DNA damage, and actively regulate the cell's response to DNA damage, including those elicited by environmental toxicants. The long term goal of this project is to understand the regulation and functions of lncRNAs in response to environmental exposures. First, we will identify lncRNAs and open chromatin sites induced by diverse genotoxic agents. Second, we will determine how the DNA damage-inducible lncRNAs modulate the activity of p53, a key transcription factor in the damage response. Third, using two new genomic technologies, we will identify the chromatin regulatory functions and gene targets of toxicant- induced lncRNAs. These experiments will provide key insights into how incipient environmental stress is transmitted into long term changes in gene expression, chromatin states, and ultimately distinct cell fates.