What is ten-eleven translocation?
Ten-eleven translocation proteins (TET1-3) are dioxygenases that oxidize 5-methyldeoxycytosine, thus taking part in passive and active demethylation. TETs have shown to be involved in immune cell development, affecting from self-renewal of stem cells and lineage commitment to terminal differentiation.
What are Tet proteins?
TET proteins are large (∼180- to 230-kDa) multidomain enzymes (Fig. 1). All TET proteins contain a conserved double-stranded β-helix (DSBH) domain, a cysteine-rich domain, and binding sites for the cofactors Fe(II) and 2-oxoglutarate (2-OG) that together form the core catalytic region in the C terminus.
What is the role of TET?
TET enzymes and oxidized 5mC derivatives play important roles in various biological and pathological processes, including regulation of DNA demethylation, gene transcription, embryonic development, and oncogenesis.
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 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.
Where are TET enzymes found?
embryonic stem cells
TET1/2 are found in embryonic stem cells, while TET3 is found in the germ line (Ito et al., 2010). The significance of these differences, and the mechanisms of how TETs are regulated remain largely unknown. The potential biological roles of these enzymes are becoming clear.
How do TET enzymes work?
A TET enzyme is an alpha-ketoglutarate (α-KG) dependent dioxygenase that catalyses an oxidation reaction by incorporating a single oxygen atom from molecular oxygen (O2) into its substrate, 5-methylcytosine in DNA (5mC), to produce the product 5-hydroxymethylcytosine in DNA.
What enzyme does Hydroxymethylation?
2.3. TET enzymes and DNA hydroxymethylation regulate brain functions
| Enzyme | KO/Kd | Phenotype |
|---|---|---|
| TET 1/2/3 | Triple Knockout | Impaired ability to differentiate into embryoid bodies and teratomas; could not support embryonic development |
How do I identify CpG islands?
Go to the UCSC genome browser gateway. On the new page,you may need to “zoom out” to see the entire gene. (At the top, right of center.) Scroll down to the line which shows “CpG islands”.
Can DNA methylation be reversed?
DNA methylation can be reversed either passively, as when maintenance DNA methyltransferase activity is inhibited in proliferating cells, or by an active, replication-independent process in which DNA methylation is enzymatically removed.
Which sources are most likely responsible for the presence of large numbers of TET enzymes in sample cells?
Which sources are most likely responsible for the presence of large numbers of Tet enzymes in sample cells? Tet enzymes are known to be responsible for the translocations found in certain types of leukemias. During implantation of the embryo, there is an abundance of methylation loss that is mediated by the Tet enzyme.
What are epigenetic targets?
As histone methyltransferase inhibitors advance through clinical trials, researchers accelerate the search for other epigenetic drug targets.