LncRNA regulation of environmental response

描述（由申请人提供）：长链非编码RNA（lncRNA）已成为基因表达和染色质状态的普遍和重要的一类调节因子。我们发现许多lncRNA是由DNA损伤诱导的，并积极调节细胞对DNA损伤的反应，包括环境毒物引起的反应。该项目的长期目标是了解lncRNA对环境暴露的调节和功能。首先，我们将确定lncRNA和开放的染色质位点诱导的不同的遗传毒性剂。其次，我们将确定DNA损伤诱导的lncRNA如何调节p53的活性，p53是损伤反应中的关键转录因子。第三，利用两种新的基因组学技术，我们将确定毒物诱导的lncRNA的染色质调控功能和基因靶点。这些实验将提供关键的见解，初期的环境压力是如何传递到基因表达，染色质状态的长期变化，并最终不同的细胞命运。

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.