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Ch. 19 - Epigenetics
Chapter 18, Problem 26

DNA methylation is commonly associated with a reduction of transcription. The following data come from a study of the impact of the location and extent of DNA methylation on gene activity in eukaryotic cells. A bacterial gene, luciferase, was inserted into plasmids next to eukaryotic promoter fragments. CpG sequences, either within the promoter and coding sequence (transcription unit) or outside of the transcription unit, were methylated to various degrees, in vitro. The chimeric plasmids were then introduced into cultured cells, and luciferase activity was assayed. These data compare the degree of expression of luciferase with differences in the location of DNA methylation [Irvine et al. (2002). Mol. and Cell. Biol. 22:6689–6696]. What general conclusions can be drawn from these data? 
Table showing the impact of DNA methylation on luciferase expression in eukaryotic cells.

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1
Examine the table to understand the relationship between DNA methylation and luciferase expression.
Note the different methylation locations: outside the transcription unit, inside the transcription unit, and the entire plasmid.
Observe the trend: as the size of the methylated patch and the number of methylated CpG sequences increase, the relative luciferase expression generally decreases.
Compare the expression levels: no methylation shows the highest expression, while methylation of the entire plasmid shows the lowest expression.
Conclude that DNA methylation, especially within the transcription unit, is associated with a significant reduction in gene expression.

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