Silencing and un-silencing of tetracycline-controlled genes in neurons.
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 (tT...
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2007-01-01
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doaj-40e1b8ed3e334b81ae0fb6e67bd9995b2020-11-25T02:27:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032007-01-0126e53310.1371/journal.pone.0000533Silencing and un-silencing of tetracycline-controlled genes in neurons.Peixin ZhuM Isabel AllerUdo BaronSidney CambridgeMelanie BausenJan HerbJürgen SawinskiAli CetinPavel OstenMark L NelsonSebastian KüglerPeter H SeeburgRolf SprengelMazahir T HasanTo 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.http://europepmc.org/articles/PMC1888723?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Peixin Zhu M Isabel Aller Udo Baron Sidney Cambridge Melanie Bausen Jan Herb Jürgen Sawinski Ali Cetin Pavel Osten Mark L Nelson Sebastian Kügler Peter H Seeburg Rolf Sprengel Mazahir T Hasan |
spellingShingle |
Peixin Zhu M Isabel Aller Udo Baron Sidney Cambridge Melanie Bausen Jan Herb Jürgen Sawinski Ali Cetin Pavel Osten Mark L Nelson Sebastian Kügler Peter H Seeburg Rolf Sprengel Mazahir T Hasan Silencing and un-silencing of tetracycline-controlled genes in neurons. PLoS ONE |
author_facet |
Peixin Zhu M Isabel Aller Udo Baron Sidney Cambridge Melanie Bausen Jan Herb Jürgen Sawinski Ali Cetin Pavel Osten Mark L Nelson Sebastian Kügler Peter H Seeburg Rolf Sprengel Mazahir T Hasan |
author_sort |
Peixin Zhu |
title |
Silencing and un-silencing of tetracycline-controlled genes in neurons. |
title_short |
Silencing and un-silencing of tetracycline-controlled genes in neurons. |
title_full |
Silencing and un-silencing of tetracycline-controlled genes in neurons. |
title_fullStr |
Silencing and un-silencing of tetracycline-controlled genes in neurons. |
title_full_unstemmed |
Silencing and un-silencing of tetracycline-controlled genes in neurons. |
title_sort |
silencing and un-silencing of tetracycline-controlled genes in neurons. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2007-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC1888723?pdf=render |
work_keys_str_mv |
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