PMID: 8943035Nov 26, 1996Paper

An upstream activator of transcription coordinately increases the level and epigenetic stability of gene expression

Proceedings of the National Academy of Sciences of the United States of America
W MagisD I Martin

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 c...Continue Reading

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Citations

Mar 21, 2000·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·S FieringD I Martin
Feb 19, 2002·Genes & Development·Yi Wei Jiang
Nov 26, 2010·The Journal of Clinical Investigation·Patrick G GallagherDavid M Bodine
Apr 7, 2006·Theoretical Biology & Medical Modelling·Qiang ZhangRory B Conolly
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·A M KringsteinH M Blau
Jun 19, 2001·The EMBO Journal·S R Biggar, G R Crabtree
May 16, 2007·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Julia M MorahanRoger Pamphlett
Aug 5, 2003·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Vladimir A BondarenkoVasily M Studitsky
Jul 25, 1998·Science·E M Blackwood, J T Kadonaga

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