Hydroxymethylation Influences on Intestinal Epithelial Cells in Health and Disease

Abstract

Epigenetics describes modiications that afect gene expression that are not encoded within the DNA sequence. DNA methylation is the longest appreciated epigenetic modiication and has been accepted to play a critical role in maintaining euchromatin and silencing genes. Recently, a separate and distinct covalent modiication has been recognized; hydroxymethylation, which has been associated with increased gene expression as opposed to gene silencing. However, traditional methods to study DNA methylation also recognized hydroxymethylation and did not distinguish between these two distinct DNA covalent modiications. Furthermore, TET enzymes have been identiied to play a critical role in active hydroxymethylation of previously methylated cytosine residues and may further result in conversion to cytosine. TET1 plays a critical role in intestinal epithelial diferentiation and development, and this is also correlated with increased hydroxymethylation in terminally diferentiated epithelial cells. Colon cancer, which arises from the colonic epithelium, exhibits decreased hydroxymethylation and altered gene expression.

Possible Therapeutics for Pseudomyxoma Peritonei: A Rare, Lethal, and the Least Investigated Disease

“…The TET methylcytosine dioxygenase family of enzymes induces active demethylation and creates a balanced methylation. 70 72…”

“…It is quite possible that induction of TET and hydroxymethylation reduces cell growth to a certain extent, but it also increases the expression of 60 % of the genes, with mucin being one of them. 72 74 So in case of PMP, TET enzymes need to be inhibited in order to reduce cancerous growth and mucin secretion.…”

“…The TET methylcytosine dioxygenase family of enzymes induces active demethylation and creates a balanced methylation. 70,72 Ten-eleven translocation enzymes oxidize 5-methylcytosine (5-mC) to 5-hydroxy-mC (5-hmC) (this is hydroxymethylation), which is modified through several suggested mechanisms including deamination and decarboxylation, ultimately leading to base-excision repair and replacement with an unmethylated cytosine. Ten-eleven translocation 1 is the most prominent member of the TET family, and previous studies showed that knockdown of TET1 results in increased global methylation in mice.…”