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Series GSE64097 Query DataSets for GSE64097
Status Public on Mar 01, 2015
Title Murine liver tissue, Mdr2-/+ control vs Mdr2-KO
Organism Mus musculus
Experiment type Methylation profiling by array
Summary Chronic liver inflammation precedes the majority of hepatocellular carcinomas (HCC). Here, we explore the connection between chronic inflammation and DNA methylation in the liver at the late precancerous stages of HCC development in Mdr2/Abcb4-knockout (Mdr2-KO) mice, a model of inflammation-mediated HCC. Using methylated DNA immunoprecipitation (MeDIP) followed by hybridization with Agilent CpG Islands (CGIs) microarrays we found specific CGIs in 76 genes which were hypermethylated in the Mdr2-KO liver compared to age-matched controls. Methylation of thirty among these genes was highly specific to the studied HCC model. We revealed that in most tested cases, the observed hypermethylation resulted from an age-dependent decrease of methylation of the specific CGIs in control livers with no decrease in mutant mice. Chronic inflammation did not change global levels of DNA methylation in Mdr2-KO liver, but caused a 2-fold decrease of the global 5-hydroxymethylcytosine level in mutants compared to controls. This decrease could result from a less efficient age-dependent demethylation of specific CpG sites in the liver of Mdr2-KO mutants, as described above. Expression of some tested hypermethylated genes was increased in Mdr2-KO livers compared to controls (28%), others were either similarly expressed (44%), or not expressed in the liver (28%). Liver cell fractionation revealed, that the relative hypermethylation of specific CGIs in Mdr2-KO compared to control livers affected either hepatocyte, or non-hepatocyte, or both fractions. There was only episodic correlation between changes of gene methylation and expression in cell fractions. Conclusion: Chronic liver inflammation causes hypermethylation of specific CGIs, which may affect both hepatocytes and non-hepatocyte liver cells. These changes may serve as markers of an increased regenerative activity and of a precancerous microenvironment in the chronically inflamed liver.
 
Overall design Two-condition experiment, Mdr2-KO vs Mdr2-/+ liver tissue from 12m-old male FVB strain mice. Biological replicates: 3 control replicates, 3 knockout replicates.
 
Contributor(s) Goldenberg D, Stoyanov E, Ludwig G
Citation(s) 25918251
Submission date Dec 11, 2014
Last update date Jun 06, 2015
Contact name Dr. Daniel Goldenberg
E-mail(s) goldenberg@hadassah.org.il
Organization name Hadassah Medical Center
Department Gene Therapy Institute
Street address Ein-Karem
City Jerusalem
ZIP/Postal code 12000
Country Israel
 
Platforms (1)
GPL7099 Agilent-015279 Mouse CpG Island ChIP-on-Chip Microarray 2x105K (Feature Number version)
Samples (6)
GSM1564281 Mdr2-/+ liver tissue control_1
GSM1564282 Mdr2-/+ liver tissue control_2
GSM1564283 Mdr2-/+ liver tissue control_3
Relations
BioProject PRJNA270110

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
GSE64097_Normalized_data_with_probenames.txt.gz 1.4 Mb (ftp)(http) TXT
GSE64097_RAW.tar 59.2 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table
Processed data are available on Series record

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