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Series GSE93135 Query DataSets for GSE93135
Status Public on Jan 13, 2017
Title Gene expression profiling of cancer cells with genetic disruption of DNA methyltransferases [Agilent-026652]
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Maximizing DNA methyltransferase (DNMT’s) inhibition for cancer therapy requires defining the roles and interactions between these enzymes for maintaining the widespread DNA methylation abnormalities in cancer. Combining genetic and shRNA depletion in colon and other cancer cells reveals that DNMT1 is extremely dominant in this maintenance, with DNMT’s 3A and 3B playing minor roles, at all genomic loci including promoters and enhancers. Reducing DNMT1 below a deep threshold level, especially at promoters, is required for reversing abnormal DNA methylation and re-expressing key tumor suppressor genes. Current DNMT inhibitors (DNMTis) are challenged, at tolerable patient doses, for achieving such reductions. We introduce a new approach in which reducing levels of the DNMT targeting protein, UHRF1, complements low DNMTi doses to DNA demethylate and reactivate expression of such genes.
 
Overall design To understand precisely how the three DNMT’s, 1, 3A, and 3B, interact for maintaining DNA methylation abnormalities in cancer. We perfomed genome-wide DNA methylation and gene expression anaylses in colon cancer and other cancer cell lines following a series of genetic and shRNA depletions of each enzyme. Our data revealed that DNMT1 overwhelmingly plays the essential maintenance role. Even with combined deletions of the proteins, lowering DNMT1 below a threshold level is required for maximal loss of DNA methylation at all genomic regions and is required for maximally reversing promoter DNA promoter DNA hypermethylation with associated re-expression of key tumor suppressor genes.
 
Contributor(s) Baylin SB, Tsai H, Cai Y
Citation(s) 28232479
Submission date Jan 04, 2017
Last update date Jan 09, 2018
Contact name Stephen B Baylin
E-mail(s) sbaylin@jhmi.edu
Organization name Johns Hopkins University
Street address 1650 Orleans St. Suite 541
City Baltimore
State/province MD
ZIP/Postal code 21209
Country USA
 
Platforms (1)
GPL13497 Agilent-026652 Whole Human Genome Microarray 4x44K v2 (Probe Name version)
Samples (8)
GSM2445311 MT1hypo
GSM2445312 HCT116.MT1sh51.d12
GSM2445313 MT1hypo.MT1sh51.d12
This SubSeries is part of SuperSeries:
GSE93136 Cancer cells with genetic disruption of DNA methyltransferases
Relations
BioProject PRJNA360119

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE93135_RAW.tar 123.3 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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