GSE118970 Defining UHRF1 Domains That Support Maintenance of Human Colon Cancer DNA Methylation and Oncogenic Properties [methylation]

Contributors : Xiangqian Kong ; Wenbing Xie ; Yong Tao ; Stephen Brown ; Yi Cai ; Michael Topper ; Ray-Whay C Yen ; Cynthia A Zahnow ; Limin Xia ; Stephen B BaylinSeries Type : Methylation profiling by arrayOrganism : Homo sapiensUHRF1 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.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Methylation profiling by array Homo sapiens Source Type: research