Transcription-dependent Dynamic Supercoiling Is a Short-Range Genomic Force

Nat Struct Mol Biol. 2013 Mar;20(3):396-403. doi: 10.1038/nsmb.2517. Epub 2013 Feb 17.

Abstract

Transcription has the capacity to mechanically modify DNA topology, DNA structure and nucleosome arrangement. Resulting from ongoing transcription, these modifications in turn may provide instant feedback to the transcription machinery. To substantiate the connection between transcription and DNA dynamics, we charted an ENCODE map of transcription-dependent dynamic supercoiling in human Burkitt's lymphoma cells by using psoralen photobinding to probe DNA topology in vivo. Dynamic supercoils spread ~1.5 kilobases upstream of the start sites of active genes. Low- and high-output promoters handled this torsional stress differently, as shown by using inhibitors of transcription and topoisomerases and by chromatin immunoprecipation of RNA polymerase and topoisomerases I and II. Whereas lower outputs are managed adequately by topoisomerase I, high-output promoters additionally require topoisomerase II. The genome-wide coupling between transcription and DNA topology emphasizes the importance of dynamic supercoiling for gene regulation.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Burkitt Lymphoma / genetics
  • Chromatin Immunoprecipitation
  • Cross-Linking Reagents
  • DNA Topoisomerases, Type I / genetics
  • DNA Topoisomerases, Type I / metabolism
  • DNA Topoisomerases, Type II / genetics
  • DNA Topoisomerases, Type II / metabolism
  • DNA, Superhelical / chemistry*
  • Ficusin / chemistry
  • Gene Expression Regulation*
  • Humans
  • Promoter Regions, Genetic
  • Transcription Initiation Site
  • Transcription, Genetic*
  • Tumor Cells, Cultured

Substances

  • Cross-Linking Reagents
  • DNA, Superhelical
  • DNA Topoisomerases, Type I
  • TOP1 protein, human
  • DNA Topoisomerases, Type II
  • Ficusin

Associated data

  • GEO/GSE43752