What is hydroxymethylation?
Modifications on the DNA regulate every part of normal cellular programming: which genes will be transcribed and form proteins, and which regions will be silenced. The most well-studied modification is DNA Methylation (5mC), which typically down-regulates or silences transcription at specific DNA loci.
Hydroxymethylation (5’hydroxy methylcytosine or 5hmC) is functionally different from conventional Methylation (5mC). The function of 5hmC is still subject of intense research, but research has shown that it is functionally distinct from 5mC. 5hmC recruits transcriptional regulators, splicing factors, DNA repair proteins and chromatin regulators that are distinct from those recruited by 5mC. It may be part of the process of active demethylation and could therefore lead to transcriptional activation.
5hmC is involved in every part of normal cellular programming. These residues are especially frequent during embryonic development, stem cell reprogramming and cellular differentiation. It has also been shown to serve as a strong biomarker in the development and progression of cancer and other diseases.
Loss of global hydroxymethylation is associated with malignant human cancers such as melanoma. Next to an important diagnostic indicator, it may serve as a prognostic marker. In many hematopoietic malignancies, mutations in TET2 are commonly observed an are associated with poor patient outcomes. Dramatic changes in total 5hmC levels have also been implicated in the progression of major neurological disorders including Alzheimer’s disease, Friedrich’s ataxia and Huntington’s disease.