Methylation in the preinitiation domain suppresses gene transcription by an indirect mechanism

Alex Levine*, Giulio L. Cantoni, Aharon Razin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Although the first observations of the inhibitory effect of methylation on gene activity were made almost a decade ago, the mechanism by which methyl groups affect transcription is still obscure. Here we use engineered promoters methylated in vitro in transient transfections to study the mechanism by which methylation mediates promoter repression. The results clearly show that the location of the methyl groups within the promoter region determines the extent of promoter repression. The most effective suppression was observed when methylation was in the preinitiation domain. The results also support a previous suggestion that a mediator protein is involved in the mechanism of promoter inhibition. The suppressor effect of methylation at sequences flanking the TATA box can be partially overcome in the presence of the simian virus 40 enhancer. In addition, results obtained by transient thymidine labeling of Ltk- cells that were transfected with a methylated thymidine kinase gene from herpes simplex virus, at the level of approximately one template per cell, further support the conclusion that methylation affects primarily transcription preinitiation.

Original languageAmerican English
Pages (from-to)10119-10123
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number21
StatePublished - 1992

Keywords

  • In vitro transcription
  • Transcription factor TFIID and TFIIA binding
  • Transcription reinitiation
  • Transient transfections

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