(228do) Memory of DNA Methylation in Live Cells Exposed to Environmental Chemicals

Exposure to heavy metals, such as lead (Pb), at an early development stage is known to be affililiated with adverse health outcomes at a late life stage. In spite of decades of efforts, the seach of molecular markers that characterize early-stage heavy metal exposure does not have any successful hits. Comparative transcriptomics study suggests that Pb exposure can trasiently alters gene expression pattern but the observed changes do not persist. Furthermore, gene sets that contribute to disease development at a late-life stage have little overlap with those identified at an early stage right after heavy metal exposure. In spite of accumulating evidence suggesting the existence of long-term cellular memory arising from previous Pb exposure, the exact molecular traits of â??memoryâ? remains unknown. Accumulating literature and our own study suggest that epigenetic changes of specific gene sets can be the major composing unit of long term memory formed due to Pb exposure. The goal of this study is thus to identify specific epigenetic traits that are induced upon Pb exposure and subsequently persist through cell cycles and divisions. We examined human cell lines exposed to Pb at different dose and duration using ChIP-qPCR assay, bisulfite sequencing along with the live-cell imaging tools developed in our laboratory. We identified several epigenetic changes that arise from Pb exposure and characterized their short- and long-term stability using a coarse-grained signaling model framework. The identified epigenetic traits can be used as a potential biomarker for characterizing individual health risk arising from previous Pb exposure.