Exploration of CTCF post-translation modifications uncovers Serine-224 phosphorylation by PLK1 at pericentric regions during the G2/M transition
- Massachusetts General Hospital, United States
- Koch Institute for Integrative Cancer Research at MIT, United States
- Cell Signaling Technologies, United States
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 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 of hundreds of genes, including p53 and p21. We have thus identified a new CTCF PTM and provided evidence of biological function.
Data availability
High-throughput sequencing data are available in the National Center for Biotechnology Information GEO repository under accession GSE119697
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High-throughput sequencing dataNCBI Gene Expression Omnibus, GSE119697.
Article and author information
Author details
Funding
Howard Hughes Medical Institute
- Jeannie T Lee
National Institutes of Health (R37-GM58839)
- Jeannie T Lee
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, del Rosario et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Exploration of CTCF post-translation modifications uncovers Serine-224 phosphorylation by PLK1 at pericentric regions during the G2/M transition
eLife 8:e42341.
https://doi.org/10.7554/eLife.42341
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