Enroth et al. BMC Cancer 2011, 11:450 http://www.biomedcentral.com/1471-2407/11/450 Page 6 of 13 Figure 4 Normal-to-tumor histone modification transitions. (A) Normal-to-tumor transition graphs detected in patient 1 separated by starting condition. The number of associated genes is given below each of the 15 monitored transitions. The 15 transitions are grouped into 3 categories given by the color of the target. Below each start condition a region-centered footprint is drawn depicting the change in signal over the detected genomic regions. The selected transitions are highlighted in bold in the graph. (B) Part of the WNT-pathway color coded by change in epigenetic markers in patient 1. Red indicate an activating change (’N -’ to ‘T K4’, ‘N K27’ to ‘T K4’ or ‘N Biv’ to ‘T K4’) while Blue indicate an repressive change (’N -’ to ‘T K27’, ‘N K4’ to ‘T K27’, ‘N K4’ to ‘T -’, ‘N K4’ to ‘T Biv’ or ‘N Biv’ to ‘T K27’). a transcription factor that has been suggested as an important factor in inducing apoptosis in mice [28], and has been shown to have predictive power on colorectal cancer recurrence in human patient cohorts [29]. A number of transitions were specific to individual patients e.g. from category iii). Some genes had H3K4me3 in normal colon which changed to H3K27me3 in tumors, e.g. in patient 1 HOXB13 and KREMEN2, which are frequently down regulated in CRC [30,31]. Among genes with a silent state (H3K27me3 mark) in normal colon that became active in CRC samples (gained H3K4me3) there were several well-characterized oncogenes [32-36], e.g. in patient 1 FLI1, WWTR1 &ZEB2 and in patient 2 TACSTD2 &TWIST1 (Figure 1A and Additional file 2, Figure S5 (patient 1)), the last two with proposed importance in CRC [32,35]. Several genes in categories i) and ii) were found to have the same transitions in both patients. Both our patients have H3K4me3 on the PTGER2 gene in normal tissue and gained H3K27me3 in the tumor, which offers a mechanistic explanation to the previously reported expression pattern [37] of this gene in colorectal cancer. In addition, three genes common to both patients which carried bivalent marks in normal and lost H3K4me3 in tumor, LHX9, PKNOX2 and LBXCOR1 and one, PRDM8, lost the H3K27me3 in tumor, all of which are transcription factors with unknown function in colon. The chromatin states of genes involved in biological pathways with relevance in CRC biology [38] was speci- fically investigated. The WNT-signalling pathway has been implicated in CRC [39,40], with the APC gene fre- quently silenced or mutated. Patient 1 has tumor repres- sive transitions in the APC gene and tumor activating