A HUSH for transgene expression

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Science  26 Jun 2015:
Vol. 348, Issue 6242, pp. 1433-1434
DOI: 10.1126/science.aac6529

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The introduction of an extra gene into a genome—transgenesis—is frequently used as an experimental approach to study gene function but also has applications in biotechnology and gene therapy efforts. In mammalian cells, transgenes are often integrated in a random manner leading to variable levels of expression, with differences as great as three orders of magnitude depending on the integration site (1). The complications of unpredictable levels of transgene expression are well recognized, but the mechanisms leading to variable expression are poorly understood. On page 1481 of this issue, Tchasovnikarova et al. (2) determine that a protein complex silences extra genes that are inserted into heterochromatin, regions of compacted DNA. This represents a new aspect of gene regulation that depends on chromatin context.