Language
English
Publication Date
8-18-2020
Journal
Scientific Reports
DOI
10.1038/s41598-020-70610-0
PMID
32811853
PMCID
PMC7435197
PubMedCentral® Posted Date
8-18-2020
PubMedCentral® Full Text Version
Post-print
Abstract
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.
Keywords
Cell Nucleus, Chromatin, Cullin Proteins, DNA-Binding Proteins, Genes, myc, HeLa Cells, Humans, Protein Binding, Protein Processing, Post-Translational, Proteolysis, Proto-Oncogene Proteins c-myc, Transcription Factors, Transcription, Genetic, Ubiquitin, Ubiquitin-Protein Ligases, Ubiquitination
Published Open-Access
yes
Recommended Citation
Sweeney, Melanie A; Iakova, Polina; Maneix, Laure; et al., "The Ubiquitin Ligase Cullin-1 Associates With Chromatin and Regulates Transcription of Specific C-MYC Target Genes" (2020). Faculty and Staff Publications. 713.
https://digitalcommons.library.tmc.edu/baylor_docs/713
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Biology Commons, Genetic Phenomena Commons, Genetic Processes Commons, Genetic Structures Commons, Medical Genetics Commons, Medical Specialties Commons