Exploration of CTCF post-translation modifications uncovers Serine-224 phosphorylation by PLK1 at pericentric regions during the G2/M transition
Name
elife-42341-v4.pdf
Description
Published version
Size
8.36 MB
Format
Adobe PDF
Checksum (MD5)
2280e8ae2e17eda0a702b4f1bca73cc6
Author(s)
Del Rosario, Amanda M
White, Forest M.
Date Issued
January 2019
Journal
eLife
Publisher
eLife Sciences Publications, Ltd
Citation
Del Rosario, Brian C. et al. “Exploration of CTCF post-translation modifications uncovers Serine-224 phosphorylation by PLK1 at pericentric regions during the G2/M transition.” eLife 8 (2019): e42341 © 2019 The Author(s)
Version
Final published version
Abstract
The zinc finger CCCTC-binding protein (CTCF) carries out many functions in the cell. Although previous studies sought to explain CTCF multivalency based on sequence composition of binding sites, few examined how CTCF post-translational modification (PTM) could contribute to function. Here, we performed CTCF mass spectrometry, identified a novel phosphorylation site at Serine 224 (Ser224-P), and demonstrate that phosphorylation is carried out by Polo-like kinase 1 (PLK1). CTCF Ser224-P is chromatin-associated, mapping to at least a subset of known CTCF sites. CTCF Ser224-P accumulates during the G2/M transition of the cell cycle and is enriched at pericentric regions. The phospho-obviation mutant, S224A, appeared normal. However, the phospho-mimic mutant, S224E, is detrimental to mouse embryonic stem cell colonies. While ploidy and chromatin architecture appear unaffected, S224E mutants differentially express hundreds of genes, including p53 and p21. We have thus identified a new CTCF PTM and provided evidence of biological function.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.7554/ELIFE.42341
