We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Preventing gene silencing with human replicators.
- Authors
Haiqing Fu; Lixin Wang; Chii-Mei Lin; Singhania, Sumegha; Bouhassira, Eric E.; Aladjem, Mirit I.
- 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.
- Subjects
GENETIC transcription; GENE therapy; DNA replication; HISTONES; ACETYLATION; TRANSGENES
- Publication
Nature Biotechnology, 2006, Vol 24, Issue 5, p572
- ISSN
1087-0156
- Publication type
Article
- DOI
10.1038/nbt1202