Preventing gene silencing with human replicators

Haiqing Fu, Lixin Wang, Chii Mei Lin, Sumegha Singhania, Eric E. Bouhassira, Mirit I. Aladjem

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)572-576
Number of pages5
JournalNature Biotechnology
Volume24
Issue number5
DOIs
StatePublished - May 2006

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Gene therapy
Gene Silencing
DNA Replication
Transgenes
Genetic Therapy
DNA
Genes
Euchromatin
Acetylation
DNA sequences
S Phase
Epigenomics
Gene expression
Histones
Chromatin
Gene Expression

ASJC Scopus subject areas

  • Microbiology

Cite this

Fu, H., Wang, L., Lin, C. M., Singhania, S., Bouhassira, E. E., & Aladjem, M. I. (2006). Preventing gene silencing with human replicators. Nature Biotechnology, 24(5), 572-576. https://doi.org/10.1038/nbt1202

Preventing gene silencing with human replicators. / Fu, Haiqing; Wang, Lixin; Lin, Chii Mei; Singhania, Sumegha; Bouhassira, Eric E.; Aladjem, Mirit I.

In: Nature Biotechnology, Vol. 24, No. 5, 05.2006, p. 572-576.

Research output: Contribution to journalArticle

Fu, H, Wang, L, Lin, CM, Singhania, S, Bouhassira, EE & Aladjem, MI 2006, 'Preventing gene silencing with human replicators', Nature Biotechnology, vol. 24, no. 5, pp. 572-576. https://doi.org/10.1038/nbt1202
Fu, Haiqing ; Wang, Lixin ; Lin, Chii Mei ; Singhania, Sumegha ; Bouhassira, Eric E. ; Aladjem, Mirit I. / Preventing gene silencing with human replicators. In: Nature Biotechnology. 2006 ; Vol. 24, No. 5. pp. 572-576.
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