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Series GSE71548 Query DataSets for GSE71548
Status Public on May 10, 2016
Title Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma [DNA methylation]
Organism Homo sapiens
Experiment type Methylation profiling by genome tiling array
Summary Chronic exposure to aflatoxin B1 (AFB1) has, in certain regions in the world, been strongly associated with the development of hepatocellular carcinoma (HCC). AFB1 is a very potent hepatotoxic and carcinogenic mycotoxin which is frequently reported as a food contaminant. Epigenetic modifications provoked by environmental exposures, such as AFB1, may create a so called persistent "epigenetic memory" or "footprint". Deregulation of epigenetic mechanisms has actually been reported in HCC patients following AFB1 exposure; however no attempts have yet been made to investigate early effects on the epigenome level which may be persistent on longer term thereby possibly initiating carcinogenic events. In this study, we aim to identify methyl DNA-mRNA-interactions representative for a persistent epigenetic "footprint" associated with the early onset of AFB1-induced HCC. For this, primary human hepatocytes were exposed to 0.3 ┬ÁM of AFB1 for 5 days. Persistent epigenetic effects were m easured 3 days after terminating the carcinogenic treatment. Whole genome DNA methylation changes and whole genome transcriptomic analysis were analyzed applying microarray technologies, and cross-omics interactions were evaluated. Upon combining transcriptomics data with results on DNA methylation, a range of persistent hyper- and hypomethylated genes was identified which appeared also affected on the transcriptome level. For six of the hypomethylated and upregulated genes, namely TXNRD1, PCNA, CCNK, DIAPH3, RAB27A and HIST1H2BF, a clear role in carcinogenic events could be identified. This study is the first to report on a carcinogen-induced persistent impact on the "epigenetic footprint" in relation with the transcriptome which could be indicative for the early onset of AFB1-related development of HCC.
Overall design The study investigated differential gene expression, microRNA expression and DNA methylation changes in a pool of primary human hepatocyte RNA after 3 days of wash out following 5 days of repetative exposure to 0.3 uM of aflatoxin B1 or DMSO. Three biological replicates per compound/solvent. In total 6 arrays.
The references 27, 28, 29, 30 and 32 are:

27. Eijssen LM, Jaillard M, Adriaens ME, Gaj S, de Groot PJ, Muller M, et al. User-friendly solutions for microarray quality control and pre-processing on Nucleic Acids Res. 2013;41(Web Server issue):W71-6.
28. Gautier L, Cope L, Bolstad BM, Irizarry RA. affy--analysis of Affymetrix GeneChip data at the probe level. Bioinformatics. 2004;20(3):307-15.
29. Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, et al. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 2004;5(10):R80.
30. Rieswijk L, Lizarraga D, Brauers KJ, Kleinjans JC, van Delft JH. Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks. Mutagenesis. 2014;29(1):17-26.
32. Coonen M, Theunissen DH, Kleinjans JC, Jennen DG. MagiCMicroRna: a web implementation of AgiMicroRna using shiny. Source code for biology and medicine. 2015;10:4

Contributor(s) Rieswijk L
Citation(s) 27153756
Submission date Jul 30, 2015
Last update date May 12, 2016
Contact name Linda Rieswijk
Organization name Maastricht University
Department Toxicogenomics
Street address Universiteitssingel 50
City Maastricht
ZIP/Postal code 6229 ER
Country Netherlands
Platforms (1)
GPL16284 NimbleGen Human DNA Methylation 2.1M Deluxe Promoter Array [100929_HG19_Deluxe_Prom_Meth_HX1]
Samples (6)
GSM1836792 PHH_WO_control_exp1 [genomic]
GSM1836793 PHH_WO_control_exp2 [genomic]
GSM1836794 PHH_WO_control_exp3 [genomic]
This SubSeries is part of SuperSeries:
GSE71549 Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma
BioProject PRJNA291516

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
GSE71548_RAW.tar 688.5 Mb (http)(custom) TAR (of PAIR)
GSE71548_WO_LD_ratios.txt.gz 117.5 Mb (ftp)(http) TXT
Processed data are available on Series record

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