: 1. DNA methylation is a critical epigenetic modification that silences gene transcription, participates in X-chromosome inactivation in females, and regulates genomic imprinting. 2. We have devised a method to inhibit transcriptional initiation by constructing short methylated oligonucleotides which induce DNA methylation at specific loci. 3. The methodology by which we devise these oligonucleotides is described, using oligonucleotides directed against the oncogene, Bcl-2.4. The human Bcl-2 gene contains two promoters, each of which contains a CpG island in its core region. Oligonucleotides are designed which can inhibit Bcl-2 transcription and lead to decreased mRNA and protein in vitro. When compared to standard anti-sense oligonucleotide action, these methylated oligonucleotides are far more sensitive and potentially, longer acting. 5. In principle, using this methodology, it should be possible to design methylated oligonucleotides that can methylate CpG islands and thereby downregulate any gene.
Directing DNA methylation to inhibit gene expression. Publishing Authors By Initials
Directing DNA methylation to inhibit gene expression. Journal Published:
PUBLICATION TYPE: Review
Journal: Cellular and molecular neurobiology
VOLUME: 26
Page Numbers: 425-38
Journal Abbreviation: Cell. Mol. Neurobiol.
ISSN: 0272-4340
DAY: 19
MONTH: 05
YEAR: 2006
Directing DNA methylation to inhibit gene expression. Information
Number of References: 44
LANGUAGE: eng
NlmUniqueID: 8200709
Directing DNA methylation to inhibit gene expression. Keywords Mesh Terms:
KEYWORDS: Proteins
MESH TERMS: genetics
Chemical & Substance for Abstract: Directing DNA methylation to inhibit gene expression. Information
Substance Name: bone growth factors
Registry Number: 0
Grant and Affiliation Information for Directing DNA methylation to inhibit gene expression.
AFFILIATION: Department of Medicine, Stanford University, Medical Service, VA Palo Alto Health Care System, Miranda Ave., Palo Alto, California 94304, USA. arhoffman@stanford.edu
Country: United States
AGENCY: United States NCI
GRANT: R43 CA86664-01
ACRONYM: CA
MEDLINETA: Cell Mol Neurobiol
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