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| Status |
Public on Feb 28, 2019 |
| Title |
Defining UHRF1 Domains That Support Maintenance of Human Colon Cancer DNA Methylation and Oncogenic Properties [methylation] |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by array
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| Summary |
UHRF1 is essential for targeting DNA methyltransferases (DNMT’s) to replicating DNA to establish de novo DNA methylation and maintain it. While, UHRF1 domains are defined, including requirement for an E3 ligase region, for de novo methylation, those essential for maintenance have been difficult to outline. Herein, via a new assay, chromatin histone-binding and a hemimethylated DNA reader domains, but not the ligase domain are found essential for cancer-specific DNA methylation maintenance in human colorectal cancer (CRC) cells. Disrupting each essential domain phenocopies UHRF1 depletion for global DNA demethylation, reactivation of tumor suppressor genes (TSGs), and reduction in CRC invasion and metastatic properties. Moreover, there is strong negative correlation between high UHRF1 expression, low TSG expression, and abnormal methylation with CRC progression and overall survival. Our battery of findings suggest the value of targeting specific domains of UHRF1 for cancer therapy and adding a precision medicine approach through use of the biomarker associations we define.
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| Overall design |
Bisulphite converted DNA from the 30 samples to test DNA methylation alterations in endogenous UHRF1 depleted HCT116 and RKO cells complemented with various domain mutants.
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| Contributor(s) |
Kong X, Xie W, Tao Y, Brown S, Cai Y, Topper M, Yen RC, Zahnow CA, Xia L, Baylin SB |
| Citation(s) |
30956060 |
| Submission date |
Aug 23, 2018 |
| Last update date |
Apr 18, 2019 |
| Contact name |
Wenbing Xie |
| E-mail(s) |
wxie6@jhmi.edu
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| Organization name |
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine
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| Department |
Department of Oncology
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| Lab |
Stephen B. Baylin
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| Street address |
1650 Orleans Street, CRB1, Room 530
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| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21205 |
| Country |
USA |
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| Platforms (1) |
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| Samples (30)
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| This SubSeries is part of SuperSeries: |
| GSE118972 |
Defining UHRF1 Domains That Support Maintenance of Human Colon Cancer DNA Methylation and Oncogenic Properties |
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| Relations |
| BioProject |
PRJNA487595 |
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