Distal enhancer regulation by promoter derepression in topologically constrained DNA in vitro

Michelle Craig Barton, Navid Madani, Beverly Emerson

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Long-range promoter-enhancer interactions are a crucial regulatory feature of many eukaryotic genes yet little is known about the mechanisms involved. Using cloned chicken β(A)-globin genes, either individually or within the natural chromosomal locus, enhancer-dependent transcription is achieved in vitro at a distance of 2 kb with developmentally staged erythroid extracts. This occurs by promoter derepression and is critically dependent upon DNA topology. In the presence of the enhancer, genes must exist in a supercoiled conformation to be actively transcribed, whereas relaxed or linear templates are inactive. Distal protein-protein interactions in vitro may be favored on supercoiled DNA because of topological constraints. In this system, enhancers act primarily to increase the probability of rapid and efficient transcription complex formation and initiation. Repressor and activator proteins binding within the promoter, including erythroid-specific GATA-1, mediate this process.

Original languageEnglish (US)
Pages (from-to)7257-7262
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number14
DOIs
Publication statusPublished - Jul 8 1997
Externally publishedYes

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Keywords

  • β-Globin gene
  • Derepression
  • DNA topology
  • Enhancers
  • GATA- 1
  • In vitro transcription

ASJC Scopus subject areas

  • General

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