Silencing and un-silencing of tetracycline-controlled genes in neurons

Zhu, P., Aller, M. I., Baron, U., Cambridge, S., Bausen, M., Herb, J., Sawinski, J., Cetin, A., Osten, P., Nelson, M. L., Kugler, S., Seeburg, P. H., Sprengel, R., Hasan, M. T. (June 2007) Silencing and un-silencing of tetracycline-controlled genes in neurons. PLoS ONE, 2 (6). e533. ISSN 1932-6203 (Electronic)

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DOI: 10.1371/journal.pone.0000533


To identify the underlying reason for the controversial performance of tetracycline (Tet)-controlled regulated gene expression in mammalian neurons, we investigated each of the three components that comprise the Tet inducible systems, namely tetracyclines as inducers, tetracycline-transactivator (tTA) and reverse tTA (rtTA), and tTA-responsive promoters (P(tets)). We have discovered that stably integrated P(tet) becomes functionally silenced in the majority of neurons when it is inactive during development. P(tet) silencing can be avoided when it is either not integrated in the genome or stably-integrated with basal activity. Moreover, long-term, high transactivator levels in neurons can often overcome integration-induced P(tet) gene silencing, possibly by inducing promoter accessibility.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > annotation > gene expression profiling annotation
organism description > animal
CSHL Authors:
Communities: CSHL labs > Osten lab
Depositing User: CSHL Librarian
Date: 21 June 2007
Date Deposited: 29 Aug 2011 22:20
Last Modified: 08 Apr 2013 14:27
PMCID: PMC1888723
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