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A new tool for Synthetic Biology

Epigenetic control of gene expression

The cells of higher eukaryotes utilize chromatin state to encode "permanent" epigenetic changes in gene expression. For example, signals received by a cell during the course of development can induce the partitioning of the genome into accessible (euchromatin) and inaccessible (heterochromatin) regions that specify the fate of that cell. This epigenetic profile, in which blocks of gene are "silenced" by heterochromatin, is stably maintained and inherited by daughter cells. Thus, chromatin state provides a higher level of gene expression control that is regional (acting on many genes at once), dominant over transcription factors, ultra-cooperative (all or none), and highly stable (memory). Engineerable control over chromatin state would clearly be a powerful tool for Synthetic Biology.

We have constructed and characterized a synthetic silencing system in S. cerevisiae in which we can inducibly silence specific loci in the genome.

This foundational technology will facilitate the construction of complex genetic circuits with memory, and has potential application in the engineering of cell differentiation in higher eukaryotes.





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