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Learn MoreIn future high-throughput transcriptomic studies, we propose that the use of cell lines nullizygous for important targets of environmental chemicals will greatly facilitate the interpretation of regulated genes. To provide proof of this concept, we generated transcript profiles from wild-type and MTF-1-null cells exposed to zinc (Zn) and six putative activators of MTF-1 generated using TempO-Seq targeted sequencing of ~3000 human genes. In the absence of chemical exposure, knockout of MTF-1 resulted in expression changes in 44 genes indicating that MTF-1 has some effect on gene expression in the absence of overt activation. Almost all of the genes regulated by Zn and phenoxybenzamine were no longer regulated in the MTF-1-null cells. For the rest of the chemicals, more than half of the genes regulated in the wild-type cells were no longer regulated in the MTF-1-null cells. These studies demonstrate that many of the changes in gene expression after exposure to the putative MTF-1 activators were MTF-1-dependent. SOURCE: J,Christopher,Corton (corton.chris@epa.gov) - MD B105-01 US-EPA
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