SA-DNAm changes, as well as age-associated DNAm changes are enriched in developmental genes, such as homeobox genes [ 12], coincide with polycomb group target genes [ 18, 19] and with specific histone marks [ 13, 20].
Moreover, the fact that the HT29 H3K27me3 profile, as compared to SW480, shows higher overlap with tissues and is enriched in developmental processes, can be explained by the fact that HT29 is a low grade CRC cell line (grade II), while SW480 is a high grade (grade III-IV), poorly differentiated and highly abnormal CRC cell line.
Additional predicted gene targets were verified to bind Oct4 in situ, and targets were found to be enriched in several developmental and molecular processes by gene ontology analysis.
Importantly, RNA-Seq data also showed that clonogenic BCs highly express SOX9 (Sex Determing Region Y- Box 9), a transcriptional factor known to be enriched in branching tips of developmental lung.
On the other hand, hydroxyproline rich glycoprotein epitopes were found to be enriched in early embryogenic cells as well as in various developmental stages of somatic embryos.
Most (54%) of the transcription factors, such as COUP-TF1, AP2REP, GCNF, PAX4, HMX1, HNF1A, LHX3, OCT1, RFX, NFYA, YY1, NKX3, MZF1, GATA1, GATA2 and RUNX1, are involved in developmental processes, and 10 of the 11 communities (communities 2, 4, 5, 7, 8, 9, 11, 12, 15, 20) are enriched in these developmental TFs.
On the other hand, α1-chimaerin, the shorter splicing variant of α2-chimaerin, is enriched in later developmental stages and is not involved in gait behavior or contextual fear learning [ 170].
Applying ChIP on ChIPtechnology, Carrell also found that in human sperm histone modifications are enriched in Hox developmental genes, which may be very important for early embryonic development [ 15], further confirming the importance of histone modifications for the early development.
Interestingly, targets of Myc or Rex1 are implicated in protein metabolism, whereas targets of the other factors are enriched in genes involved in developmental processes.
Results are shown inAdditional file 6. Restricting ourselves to Gene Ontology (GO) biological processes associated to at least 20 genes, we found that the large cluster 1 is mostly enriched in genes involved in metabolic processes, while the cancer-specific cluster 3up is enriched in genes involved in developmental processes.
