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.

Public Health Relevance

Exposures to environmental toxins can lead to long term consequences months or years after the exposure. A new type of genes termed long noncoding RNAs (lncRNAs) are induced by cellular stress and program long term changes to how genes can be accessed. Research into lncRNAs function in environmental response will improve understanding the health impacts of environmental exposures, and ultimately how to correct them.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
1R01ES023168-01
Application #
8582263
Study Section
Special Emphasis Panel (ZES1-LWJ-D (TG))
Program Officer
Tyson, Frederick L
Project Start
2013-08-20
Project End
2017-05-31
Budget Start
2013-08-20
Budget End
2014-05-31
Support Year
1
Fiscal Year
2013
Total Cost
$564,684
Indirect Cost
$203,476
Name
Stanford University
Department
Dermatology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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Quinn, Jeffrey J; Ilik, Ibrahim A; Qu, Kun et al. (2014) Revealing long noncoding RNA architecture and functions using domain-specific chromatin isolation by RNA purification. Nat Biotechnol 32:933-40
Li, Lingjie; Chang, Howard Y (2014) Physiological roles of long noncoding RNAs: insight from knockout mice. Trends Cell Biol 24:594-602