Cancer associated epigenetic transitions identified by genome-wide histone methylation binding profiles in human colorectal cancer samples and paired normal mucosa.
BACKGROUND
Despite their well-established functional roles, histone modifications have received less attention than DNA methylation in the cancer field. In order to evaluate their importance in colorectal cancer (CRC), we generated the first genome-wide histone modification profiles in paired normal colon mucosa and tumor samples.


METHODS
Chromatin immunoprecipitation and microarray hybridization (ChIP-chip) was used to identify promoters enriched for histone H3 trimethylated on lysine 4 (H3K4me3) and lysine 27 (H3K27me3) in paired normal colon mucosa and tumor samples from two CRC patients and for the CRC cell line HT29.


RESULTS
By comparing histone modification patterns in normal mucosa and tumors, we found that alterations predicted to have major functional consequences were quite rare. Furthermore, when normal or tumor tissue samples were compared to HT29, high similarities were observed for H3K4me3. However, the differences found for H3K27me3, which is important in determining cellular identity, indicates that cell lines do not represent optimal tissue models. Finally, using public expression data, we uncovered previously unknown changes in CRC expression patterns. Genes positive for H3K4me3 in normal and/or tumor samples, which are typically already active in normal mucosa, became hyperactivated in tumors, while genes with H3K27me3 in normal and/or tumor samples and which are expressed at low levels in normal mucosa, became hypersilenced in tumors.


CONCLUSIONS
Genome wide histone modification profiles can be used to find epigenetic aberrations in genes associated with cancer. This strategy gives further insights into the epigenetic contribution to the oncogenic process and may identify new biomarkers.
The Linnaeus Centre for Bioinformatics, Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Sweden.
Stefan
S
Enroth
Alvaro
A
Rada-Iglesisas
Robin
R
Andersson
Ola
O
Wallerman
Alkwin
A
Wanders
Lars
L
Påhlman
Jan
J
Komorowski
Claes
C
Wadelius
D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005753:Gastric Mucosa / Q000378:metabolism; D020869:Gene Expression Profiling; D016678:Genome; D055106:Genome-Wide Association Study; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D011401:Promoter Regions, Genetic
D006657:Histones