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An upstream activator of transcription coordinately increases the level and epigenetic stability of gene expression.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 1996 Nov 26; Vol. 93 (24), pp. 13914-8. - Publication Year :
- 1996
-
Abstract
- The mouse metallothionein-I (mMT-I) promoter is activated by the metal response element-binding transcription factor (MTF), which binds metal response elements (MREs) when stimulated with heavy metals. We analyzed eight K562 erythroleukemia cell clones, each carrying a single integrated copy of an mMT-I/beta-geo construct, using a system that can independently assess the level of beta-geo expression and the rate at which it is silenced. In these clones, basal expression and rate of silencing vary widely and independently with integration site. This implies that the rates of transcription and of silencing are separate properties determined by interaction of the regulatory elements of the transgene with the site of integration. Induction of the mMT-I promoter with zinc both increases expression level and strongly retards silencing of beta-geo expression. At a given integration site, expression level and silencing are affected coordinately by induction. Taken together with earlier studies of distant metal-responsive elements, these results suggest that distance from the promoter may determine whether a factor can increase transcription rate. Stimulation of an MRE can both increase transcription and overcome repressive effects of chromatin; we suggest that these functions are linked.
- Subjects :
- Animals
Cell Line
Gene Expression Regulation drug effects
Humans
Leukemia, Erythroblastic, Acute
Mice
Recombinant Proteins biosynthesis
Transfection
Tumor Cells, Cultured
Zinc pharmacology
beta-Galactosidase biosynthesis
Metallothionein biosynthesis
Metallothionein genetics
Promoter Regions, Genetic
Regulatory Sequences, Nucleic Acid
Transcription, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 93
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 8943035
- Full Text :
- https://doi.org/10.1073/pnas.93.24.13914