Transcription factor NF-κB unravels nucleosomes

Tommy Stormberg, Shaun Filliaux, Hannah E.R. Baughman, Elizabeth A. Komives, Yuri L. Lyubchenko

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

NF-κB is a transcription factor responsible for activating hundreds of genes in mammalian organisms. To accomplish its function, NF-κB must interact with DNA occupied by nucleosomes, but how this interaction occurs is unclear. Here we used Atomic Force Microscopy to characterize complexes of NF-κB with nucleosomes assembled on different DNA templates. The assembly of NF-κB-nucleosome complexes leads to a substantial decrease of DNA wrapping efficiency from 149 ± 2 bp (SEM) for the control nucleosome sample to 135 ± 3 bp for complexes of nucleosomes with NF-κB. Mapping of the nucleosomes did not reveal displacement of under-wrapped nucleosomes from their original position, suggesting that unravelling involves dissociation of one or both flanks of the nucleosomes. Binding of NF-κB to the core was identified by nucleosome core volume measurements. We discovered two binding modes of NF-κB associated with nucleosome unravelling - NF-κB bound to the nucleosome core and to the DNA flanks. From these findings we propose two models explaining the interaction of NF-κB with the nucleosome complex. The partial unravelling of nucleosomes by NF-κB makes the DNA segment at the edge of the nucleosome core accessible, facilitating the transcription process. We speculate that NF-κB can function as a pioneer factor, enhancing its ability to facilitate rapid transcriptional response to cell stress.

Original languageEnglish (US)
Article number129934
JournalBiochimica et Biophysica Acta - General Subjects
Volume1865
Issue number9
DOIs
StatePublished - Sep 2021

Keywords

  • AFM
  • Atomic force microscopy
  • Chromatin
  • Pioneer factors
  • Protein interaction
  • Transcription factors

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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