The ubiquitin ligase Cullin-1 associates with chromatin and regulates transcription of specific c-MYC target genes

Sci Rep. 2020 Aug 18;10(1):13942. doi: 10.1038/s41598-020-70610-0.


Transcription is regulated through a dynamic interplay of DNA-associated proteins, and the composition of gene-regulatory complexes is subject to continuous adjustments. Protein alterations include post-translational modifications and elimination of individual polypeptides. Spatially and temporally controlled protein removal is, therefore, essential for gene regulation and accounts for the short half-life of many transcription factors. The ubiquitin-proteasome system is responsible for site- and target-specific ubiquitination and protein degradation. Specificity of ubiquitination is conferred by ubiquitin ligases. Cullin-RING complexes, the largest family of ligases, require multi-unit assembly around one of seven cullin proteins. To investigate the direct role of cullins in ubiquitination of DNA-bound proteins and in gene regulation, we analyzed their subcellular locations and DNA-affinities. We found CUL4A and CUL7 to be largely excluded from the nucleus, whereas CUL4B was primarily nuclear. CUL1,2,3, and 5 showed mixed cytosolic and nuclear expression. When analyzing chromatin affinity of individual cullins, we discovered that CUL1 preferentially associated with active promoter sequences and co-localized with 23% of all DNA-associated protein degradation sites. CUL1 co-distributed with c-MYC and specifically repressed nuclear-encoded mitochondrial and splicing-associated genes. These studies underscore the relevance of spatial control in chromatin-associated protein ubiquitination and define a novel role for CUL1 in gene repression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Nucleus / metabolism
  • Chromatin / metabolism*
  • Cullin Proteins / genetics*
  • Cullin Proteins / metabolism*
  • DNA-Binding Proteins
  • Genes, myc
  • HeLa Cells
  • Humans
  • Protein Binding
  • Protein Processing, Post-Translational
  • Proteolysis
  • Proto-Oncogene Proteins c-myc / genetics*
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination


  • Chromatin
  • Cullin 1
  • Cullin Proteins
  • DNA-Binding Proteins
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • Transcription Factors
  • Ubiquitin
  • Ubiquitin-Protein Ligases