Epigenetic gene inactivation induced by a cis-acting methylation center

P. Mummaneni, K. A. Walker, P. L. Bishop, M. S. Turker

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

In this report we test the hypothesis that a cis-acting methylation center can induce epigenetic gene inactivation. The cis-acting element used is an 838-base pair fragment that was shown previously to provide a de novo methylation signal (Mummaneni, P., Bishop, P. L., and Turker, M. S. (1993) J. Biol. Chem. 268, 552-558). Its normal location is approximately 1.3 kilobase pairs upstream of the mouse aprt (adenine phosphoribosyltransferase) gene. To determine if the methylation center could induce inactivation of the aprt gene, a plasmid construct was created in which the methylation center was moved next to the aprt promoter. Transfection experiments demonstrated inactivation of the aprt gene on the hybrid construct. The inactivation event was shown with a Southern blot analysis to correlate with hypermethylation and to be reversible by treatment with 2-deoxy-5'-azacytidine, a demethylating agent. Interestingly, gene inactivation induced by the methylation center required truncation of the aprt promoter. The results demonstrate that epigenetic gene inactivation can be induced by a DNA methylation center.

Original languageEnglish (US)
Pages (from-to)788-792
Number of pages5
JournalJournal of Biological Chemistry
Volume270
Issue number2
DOIs
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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