Integrative genomic analysis on the role of lncRNAs in the DNA damage response to

Harvard University, Cambridge MA

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Abstract

DESCRIPTION (provided by applicant) Exposure to environmental toxins threatens the integrity of the genome by causing mutations that can perturb the carefully regulated expression of genes. When toxins damage DNA, the cell launches a response to pause potentially affected processes and attempt repair. Thus, the DNA damage response (DDR) involves a shift in gene expression state; these shifts are typically orchestrated by epigenetic changes to the genome. Indeed, modifications to chromatin are required to launch the DDR gene expression program. In many diverse cellular processes, long noncoding RNAs (lncRNAs) have been recently shown to play an important role in chromatin modification by binding and localizing chromatin-modifying proteins. IncRNAs are a huge new class of genes whose functional mechanisms are an area of active research. Here, the investigators will perform integrative analysis of diverse genome-wide experimental datasets to place lncRNAs into chromatin modification pathways in the DDR and describe their functional mechanisms via RNA motifs. Specifically, the investigators' research has the following aims: 1) Discover lncRNAs important to the DDR via RNA sequencing throughout a time course after environmental toxin exposure. 2) Annotate DDR dynamics of genome-wide chromatins states and lncRNA-protein interactions using quantitative sequencing assays throughout a time course after environmental toxin exposure. 3) Integrate lncRNA-chromatin data to describe lncRNA motifs and chromatin modification mechanisms in the DDR. Successful completion of these aims will produce a more detailed understanding of the entities and mechanisms executing the chromatin modification processes in the DDR. The computational methods developed will be widely applicable for future integrative computational biology analyses in any cellular context.