User:Xiang Chen/Sandbox 1: Difference between revisions
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All three TET enzymes and their isoforms are involved in the biochemical pathway that converts 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). They also regulate the further conversions of 5hmC to 5-formylcytosine (5fC) and then 5fC to 5-carboxylcytosine (5caC).<ref name='He et al.'>DOI: 10.1126/science.1210944</ref> Although experimental data shows that TET3 does so to a lesser extent than TET1 and TET2.<ref name='He et al.' /> | All three TET enzymes and their isoforms are involved in the biochemical pathway that converts 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). They also regulate the further conversions of 5hmC to 5-formylcytosine (5fC) and then 5fC to 5-carboxylcytosine (5caC).<ref name='He et al.'>DOI: 10.1126/science.1210944</ref> Although experimental data shows that TET3 does so to a lesser extent than TET1 and TET2.<ref name='He et al.' /> | ||
While the oxidation performed by TET enzymes was originally thought to be a source of DNA damage, new research has implied that this catalytic activity may actually be the initial steps of a process of DNA demethylation. This hypothesized DNA demethylation pathway starts with the conversion of 5mC to 5caC after several rounds of oxidation by TET enzymes. The next step is the removal of the modified cytosine base by thymine DNA glycosylase (TDG) which leaves an abasic site on the DNA. The last step is then the process of base excision repair in which a new unmodified cytosine is regenerated at the site, thus completing the process of DNA demethylation.<ref name='He et al.' /><ref name='Rahul M. Kohli | While the oxidation performed by TET enzymes was originally thought to be a source of DNA damage, new research has implied that this catalytic activity may actually be the initial steps of a process of DNA demethylation. This hypothesized DNA demethylation pathway starts with the conversion of 5mC to 5caC after several rounds of oxidation by TET enzymes. The next step is the removal of the modified cytosine base by thymine DNA glycosylase (TDG) which leaves an abasic site on the DNA. The last step is then the process of base excision repair in which a new unmodified cytosine is regenerated at the site, thus completing the process of DNA demethylation.<ref name='He et al.' /><ref name='Rahul M. Kohli and Yi Zhang'>DOI 10.1038/nature12750</ref> | ||
===Specific Functions=== | ===Specific Functions=== | ||
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TET2 is broadly expressed, but it is especially highly expressed in hematopoietic cells, which develop into blood cells. Regarding this, it is suggested that TET2 plays a role in hematopoiesis due to the presence of TET2 mutations in many myelodysplastic syndromes.<ref>DOI 10.1182/blood-2009-03-210039</ref><ref>DOI 10.1056/NEJMoa0810069</ref><ref>DOI 10.1038/ng.391</ref> | TET2 is broadly expressed, but it is especially highly expressed in hematopoietic cells, which develop into blood cells. Regarding this, it is suggested that TET2 plays a role in hematopoiesis due to the presence of TET2 mutations in many myelodysplastic syndromes.<ref>DOI 10.1182/blood-2009-03-210039</ref><ref>DOI 10.1056/NEJMoa0810069</ref><ref>DOI 10.1038/ng.391</ref> | ||
TET3 is highly expressed in zygotes and is involved with epigenetic chromatin reprogramming in the zygote after fertilization. Specifically, it plays a role in DNA demethylation of the paternal pronucleus before implantation.<ref name='Rahul M. Kohli | TET3 is highly expressed in zygotes and is involved with epigenetic chromatin reprogramming in the zygote after fertilization. Specifically, it plays a role in DNA demethylation of the paternal pronucleus before implantation.<ref name='Rahul M. Kohli and Yi Zhang' /> | ||
== Disease == | == Disease == | ||
