Abstract:
:Transcriptional silencing, one of the major impediments to gene therapy in humans, is often accompanied by replication during late S-phase. We report that transcriptional silencing and late replication were prevented by DNA sequences that can initiate DNA replication (replicators). When replicators were included in silencing-prone transgenes, they did not undergo transcriptional silencing, replicated early and maintained histone acetylation patterns characteristic of euchromatin. A mutant replicator, which could not initiate replication, could not prevent gene silencing and replicated late when included in identical transgenes and inserted at identical locations. These observations suggest that replicators introduce epigenetic chromatin changes that facilitate initiation of DNA replication and affect gene silencing. Inclusion of functional replicators in gene therapy vectors may provide a tool for stabilizing gene expression patterns.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Fu H,Wang L,Lin CM,Singhania S,Bouhassira EE,Aladjem MIdoi
10.1038/nbt1202subject
Has Abstractpub_date
2006-05-01 00:00:00pages
572-6issue
5eissn
1087-0156issn
1546-1696pii
nbt1202journal_volume
24pub_type
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