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Nuclear microenvironments modulate transcription from low-affinity enhancers.

Albert Tsai1, Anand K Muthusamy1, Mariana Rp Alves2

  • 1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.

Elife
|November 3, 2017
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Summary
This summary is machine-generated.

Transcription factors like Ultrabithorax (Ubx) use high-concentration nuclear microenvironments to efficiently regulate genes, even with brief DNA interactions. This mechanism may apply broadly to eukaryotic gene expression.

Keywords:
D. melanogasterHox genesbiophysicschromosomesgeneslive imagingstructural biologysuper resolutiontranscription factorstranscriptional enhancers

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Area of Science:

  • Molecular Biology
  • Genetics
  • Developmental Biology

Background:

  • Transcription factors bind DNA transiently at low-affinity sites.
  • The mechanism for efficient transcription from brief, low-affinity interactions remains unclear.

Purpose of the Study:

  • To investigate how transcription factors utilize low-affinity binding sites for efficient gene regulation.
  • To explore the role of nuclear microenvironments in transcription.

Main Methods:

  • Studied Ultrabithorax (Ubx) transcription factor binding in *Drosophila melanogaster*.
  • Analyzed the *shavenbaby* (svb) locus and related enhancers.
  • Manipulated enhancer affinity and measured Ubx and Homothorax (Hth) concentrations.

Main Results:

  • Ubx utilizes low-affinity sites within nuclear microenvironments of high Ubx concentration.
  • Enhancers colocalized to these microenvironments regardless of chromosomal location.
  • Lower enhancer affinity required higher Ubx concentration for activation.
  • Homothorax (Hth) co-enriched with Ubx near Hth-dependent enhancers.

Conclusions:

  • Nuclear microenvironments with high transcription factor and cofactor concentrations can overcome kinetic inefficiency of low-affinity binding sites.
  • These microenvironments may be a general mechanism for eukaryotic transcriptional regulation.