Chromatin interaction mechanism of transcriptional control in vivo

EMBO J. 1998 Oct 15;17(20):6020-7. doi: 10.1093/emboj/17.20.6020.

Abstract

We have used a kinetic analysis to distinguish possible mechanisms of activation of transcription of the different genes in the human beta globin locus. Based on in situ studies at the single-cell level we have previously suggested a dynamic mechanism of single genes alternately interacting with the locus control region (LCR) to activate transcription. However, those steady-state experiments did not allow a direct measurement of the dynamics of the mechanism and the presence of loci with in situ primary transcript signals from two beta-like genes in cis has left open the possibility that multiple genes in the locus could initiate transcription simultaneously. Kinetic assays involving removal of a block to transcription elongation in conjunction with RNA FISH show that multiple beta gene primary transcript signals in cis represent a transition between alternating transcriptional periods of single genes, supporting a dynamic interaction mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding, Competitive / genetics
  • Cells, Cultured
  • Chromatin / genetics*
  • Chromatin / metabolism
  • Dactinomycin / pharmacology
  • Dichlororibofuranosylbenzimidazole / pharmacology
  • Fetus
  • Globins / genetics
  • Globins / metabolism
  • Humans
  • In Situ Hybridization, Fluorescence
  • Kinetics
  • Liver
  • Locus Control Region / drug effects
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / physiology*

Substances

  • Chromatin
  • Nucleic Acid Synthesis Inhibitors
  • Dactinomycin
  • Dichlororibofuranosylbenzimidazole
  • Globins