What is 5mC and 5hmC?
5hmC is the first oxidative product in the active demethylation of 5-methylcytosine (5mC). The three Ten-eleven translocation (TET) enzymes oxidize each step in the demethylation of 5mC. 5mC is first converted to 5hmC, then 5-formylcytosine (5fC), then 5-carboxylcytosine (5caC), each by TET1-3 (Ito et al., 2011).
How does 5hmC affect transcription?
5hmC is a stable mark that is commonly associated with transcriptional activation. In addition, the deregulation of 5hmC in specific regions of the genome, such as enhancers, promoters, and body of the gene, alters the expression of genes in cancer.
What is DNA Hydroxymethylation?
DNA hydroxymethylation, is a recently identified type of DNA modification in which the hydrogen atom at the C5-position in cytosine is replaced by a hydroxymethyl group, and whose, importance to biology and its role as an epigenetic marker have only been appreciated during the past few years.
What are Tet proteins?
The Ten-eleven translocation (TET) family proteins are evolutionarily conserved dioxygenases responsible for the conversion of 5-methylcytosine to 5-hydroxymethylcytosine, thereby promoting DNA demethylation. There are three members in this family, namely TET1, TET2, and TET3.
What does DNA demethylation do?
Active DNA demethylation refers to an enzymatic process that removes or modifies the methyl group from 5mC. By contrast, passive DNA demethylation refers to loss of 5mC during successive rounds of replication in the absence of functional DNA methylation maintenance machinery.
Which is the substitute of cytosine in DNA?
We investigated phage T4 as a model system, where cytosine is replaced with glucosyl-hydroxymethylcytosine (glc-HMC). We first quantified the extent and distribution of covalent modifications in T4 DNA by single-molecule DNA sequencing and enzymatic probing.
Why is cytosine only methylated?
Methylated sensitive restriction enzymes work by cleaving specific CpG, cytosine and guanine separated by only one phosphate group, recognition sites when the CpG is methylated. In contrast, unmethylated cytosines are transformed to uracil and in the process, methylated cytosines remain methylated.
Why is cytosine methylated?
Cytosine methylation affects the accessibility of the genomic regions to regulatory proteins/protein complexes, which influences chromatin structure and/or affects the rate of transcription of the gene. Cytosine methylation is the only well-studied DNA modification with established maintenance mechanisms.