Enroth et al. BMC Cancer 2011, 11:450 http://www.biomedcentral.com/1471-2407/11/450 R E S E A R C H A R T I C L E Open Access Cancer associated epigenetic transitions identified by genome-wide histone methylation binding profiles in human colorectal cancer samples and paired normal mucosa Stefan Enroth1,5†, Alvaro Rada-Iglesisas1,2,6†, Robin Andersson1,7, Ola Wallerman2, Alkwin Wanders2, Lars Påhlman3, Jan Komorowski1,4 and Claes Wadelius2* Abstract 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. Background Cancer has been traditionally considered a genetic and cytogenetic disease, but recent years have brought epige- netics to the forefront of cancer research [1,2]. Altered DNA methylation is nowadays considered a hallmark of neoplasia, including two different phenomena in cancer cells: global hypomethylation and CpG-promoter hyper- methylation of tumor suppressor genes [1,2]. The * Correspondence: claes.wadelius@igp.uu.se † Contributed equally 2Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, SE-75185 Uppsala, Sweden Full list of author information is available at the end of the article importance of epigenetic alterations in cancer is further highlighted by their use in diagnosis and by the develop- ment of new therapeutic strategies aiming at correcting them [3]. Although histone modifications play major roles in processes such as transcription, replication and DNA repair, their oncogenic importance is not yet well estab- lished. However, several lines of evidence suggest that alterations in histone modifications are crucial in cancer development and progression. Global changes in histone H4 modifications seem to be universal markers of malignant transformation [4], while other histone marks predict the prognosis of prostate cancer [5]. Two of the © 2011 Enroth et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.