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Series GSE62695 Query DataSets for GSE62695
Status Public on Feb 13, 2015
Title Genome-wide maps of RNAPII Ser5(P) in HEK 293T cells after treatment with 5-aza-CdR
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary DNA methylation can be abnormally regulated in human disease and associated with effects on gene transcription that appear to be causally related to pathogenesis. The potential to use pharmacological agents that reverse this dysregulation is therefore an attractive possibility. To test how 5-aza-2’-deoxycytidine (5-aza-CdR) influences the genome therapeutically, we exposed non-malignant cells in culture to the agent and used genome-wide assays to assess the cellular response. We found that cells allowed to recover from 5-aza-CdR treatment only partially recover DNA methylation levels, retaining an epigenetic “imprint” of drug exposure. We show very limited transcriptional responses to demethylation of not only protein-coding genes but also loci encoding non-coding RNAs, with a limited proportion of the induced genes acquiring new promoter activation within gene bodies. The data revealed an uncoupling of DNA methylation effects at promoters, with demethylation mostly unaccompanied by transcriptional changes. The limited panel of genes induced by 5-aza-CdR resembles those activated in other human cell types exposed to the drug, and represents loci targeted for Polycomb-mediated silencing in stem cells, suggesting a model for the therapeutic effects of the drug. Our results do not support the hypothesis of DNA methylation having a predominant role to regulate transcriptional noise in the genome, and indicate that DNA methylation acts only as part of a larger complex system of transcriptional regulation. The targeting of 5-aza-CdR effects with its clastogenic consequences to euchromatin raises concerns that the use of 5-aza-CdR has innate tumorigenic consequences, requiring its cautious use in diseases involving epigenetic dysregulation.
Overall design Examination of RNAPII Ser5(P) localization by ChIP-seq in HEK 293T cell after treatment with 5-aza-CdR.
Contributor(s) Ramos M, Wijetunga NA, McLellan AS, Suzuki M, Greally JM
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Submission date Oct 24, 2014
Last update date May 15, 2019
Contact name Maria-Paz Ramos
Organization name Albert Einstein College of Medicine
Department Genetics
Lab John Greally
Street address 1301 Morris Park Ave, Price 314
City Bronx
State/province New York
ZIP/Postal code 10461
Country USA
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (4)
GSM1531547 Input_DNA_Control
GSM1531548 Input_DNA_Treatment
GSM1531549 RNAPII-Ser5(P)_ChIPSeq_Control
This SubSeries is part of SuperSeries:
GSE62590 DNA demethylation by 5-aza-2'-deoxycytidine is imprinted targeted to euchromatin and has limited transcriptional consequences
BioProject PRJNA264830
SRA SRP049249

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
GSE62695_RAW.tar 910.0 Kb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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