Epigenetic signaling and crosstalk in regulation of gene expression and disease progression.

Chromatin modifications - including DNA methylation, modification of histones and recruitment of noncoding RNAs - are essential epigenetic events. Multiple sequential modifications converge into a complex epigenetic landscape. For example, promoter DNA methylation is recognized by MeCP2/methyl CpG binding domain proteins which further recruit SETDB1/SUV39 to attain a higher order chromatin structure by propagation of inactive epigenetic marks like H3K9me3. Many studies with new information on different epigenetic modifications and associated factors are available, but clear maps of interconnected pathways are also emerging. This review deals with the salient epigenetic crosstalk mechanisms that cells utilize for different cellular processes and how deregulation or aberrant gene expression leads to disease progression.

Epigenetic Regulation and Promising Therapies in Colorectal Cancer.

The recent developments in epigenetics have shown a very important role of epigenetic changes in cancer initiation, development, and progression. Some of the important histone modifications shown to occur are methylation, acetylation, phosphorylation, citrullination, sumoylation, ADP ribosylation, deamination, ubiquitination, formylation, O-GlcNAcylation, propionylation, butyrylation, proline isomerization, and crotonylation, but most of the studies in the past had limited their interest mainly on histone methylation, acetylation, and phosphorylation. Modification of DNA strands by hypermethylation and hypomethylation regulates genomic instability and promotes cancer. Colorectal cancer involves multiple changes in epigenetic marks present on histone residues and DNA, which in collaboration with genetic changes, leads to cancer progression. In this review paper, basic concepts of epigenetics relevant to cancer development are discussed, followed by its significance in understanding the mechanism of colon carcinogenesis. Some of the epigenetic target-based drugs are also discussed in the relevant sections to give an idea of the potential promises of epigenetics for colorectal cancer treatment.