Zbtb7a is a transducer for the control of promoter accessibility by NF-kappa B and multiple other transcription factors

PLoS Biol. 2018 May 29;16(5):e2004526. doi: 10.1371/journal.pbio.2004526. eCollection 2018 May.

Abstract

Gene expression in eukaryotes is controlled by DNA sequences at promoter and enhancer regions, whose accessibility for binding by regulatory proteins dictates their specific patterns of activity. Here, we identify the protein Zbtb7a as a factor required for inducible changes in accessibility driven by transcription factors (TFs). We show that Zbtb7a binds to a significant fraction of genomic promoters and enhancers, encompassing many target genes of nuclear factor kappa B (NFκB) p65 and a variety of other TFs. While Zbtb7a binding is not alone sufficient to directly activate promoters, it is required to enable TF-dependent control of accessibility and normal gene expression. Using p65 as a model TF, we show that Zbtb7a associates with promoters independently of client TF binding. Moreover, the presence of prebound Zbtb7a can specify promoters that are amenable to TF-induced changes in accessibility. Therefore, Zbtb7a represents a widely used promoter factor that transduces signals from other TFs to enable control of accessibility and regulation of gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Binding Sites
  • DNA-Binding Proteins / metabolism*
  • Enhancer Elements, Genetic
  • Isotope Labeling
  • Mice
  • Mice, Knockout
  • Promoter Regions, Genetic*
  • Transcription Factor RelA / metabolism*
  • Transcription Factors / metabolism*
  • Transcriptional Activation*

Substances

  • DNA-Binding Proteins
  • Rela protein, mouse
  • Transcription Factor RelA
  • Transcription Factors
  • Zbtb7a protein, mouse

Grants and funding

Conacyt. Fellowship for JMRP. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Ligue National Contre le Cancer. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Max Planck Society. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Fondation ARC. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.