Intest Res.  2015 Apr;13(2):112-121. 10.5217/ir.2015.13.2.112.

Epigenetic Alterations in Inflammatory Bowel Disease and Cancer

• Yi JM
• Kim TO

• KMID: 2284877
• DOI: http://doi.org/10.5217/ir.2015.13.2.112

Abstract

Overwhelming evidences supports the idea that inflammatory bowel disease (IBD) is caused by a complex interplay between genetic alterations of multiple genes and an aberrant interaction with environmental factors. There is growing evidence that epigenetic factors can play a significant part in the pathogenesis of IBD. Significant effort has been invested in uncovering genetic and epigenetic factors, which may increase the risk of IBD, but progress has been slow, and few IBD-specific factors have been detected so far. It has been known for decades that DNA methylation is the most well studied epigenetic modification, and analysis of DNA methylation is leading to a new generation of cancer biomarkers. Therefore, in this review, we summarize the role of DNA methylation alteration in IBD pathogenesis, and discuss specific genes or genetic loci using recent molecular technology advances. Here, we suggest that DNA methylation should be studied in depth to understand the molecular pathways of IBD pathogenesis, and discuss epigenetic studies of IBD that may have a significant impact on the field of IBD research.

Keyword

Inflammatory bowel diseases; Neoplasms; Epigenomics; DNA methylation

MeSH Terms

Biomarkers
DNA Methylation
Epigenomics*
Genetic Loci
Inflammatory Bowel Diseases*

Figure

• 

  Fig. 1 Methylation patterns between normal cells and tumor cells. (A) Conversion of cytosine to 5-methylcytosine by DNA methyltransferase (DNMT). DNMT catalyzes the transfer of a methyl group (CH3) from Sadenosylmethionine (SAM) to the 5-carbon position of cytosine. (B) Methylation patterns between normal cells and tumor cells. In normal cells, cytosine-phospho-guanine (CpG) sites are globally methylated which means most CpG sites outside CpG islands are methylated (black circles), whereas most CpG island sites in gene expression promoters are unmethylated (white circles). Therefore, unmethylation status of CpG islands in gene promoters permits active gene expression. In cancer cells, CpG islands in gene promoter regions become abnormally methylated and this causes transcriptional silencing of genes. Circles indicate CpG dinucleotides.

• 

  Fig. 2 Methylation level of candidate genes in IBD patients. DNA methylation of several candidate genes has been detected in UC tissues, CD tissues, and CD patient blood samples. The graph was quoted and modified from our previous publications (UC data from Kim et al.,43 2013 and CD data from Bae et al.,47 2014). CRC, colorectal cancer; TCERG1L, transcription elongation regulator 1-like; SFRP1, secreted frizzled-related protein 1; FBN2, fibrillin 2; TFPI2, tissue factor pathway inhibitor 2.

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