Preventing gene silencing with human replicators.

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 Biotechnol

journal_title

Nature biotechnology

authors

Fu H,Wang L,Lin CM,Singhania S,Bouhassira EE,Aladjem MI

doi

10.1038/nbt1202

subject

Has Abstract

pub_date

2006-05-01 00:00:00

pages

572-6

issue

5

eissn

1087-0156

issn

1546-1696

pii

nbt1202

journal_volume

24

pub_type

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