Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates.
5-Hydroxymethylcytosine (hmC) was recently detected as the sixth base in mammalian tissue at so far controversial levels. The function of the modified base is currently unknown, but it is certain that the base is generated from 5-methylcytosine (mC). This fuels the hypothesis that it represents an i...
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2010
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oai:doaj.org-article:72cdefff31ae431fab6f24a71e79a6072021-11-18T07:01:13ZTissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates.1932-620310.1371/journal.pone.0015367https://doaj.org/article/72cdefff31ae431fab6f24a71e79a6072010-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21203455/?tool=EBIhttps://doaj.org/toc/1932-62035-Hydroxymethylcytosine (hmC) was recently detected as the sixth base in mammalian tissue at so far controversial levels. The function of the modified base is currently unknown, but it is certain that the base is generated from 5-methylcytosine (mC). This fuels the hypothesis that it represents an intermediate of an active demethylation process, which could involve further oxidation of the hydroxymethyl group to a formyl or carboxyl group followed by either deformylation or decarboxylation. Here, we use an ultra-sensitive and accurate isotope based LC-MS method to precisely determine the levels of hmC in various mouse tissues and we searched for 5-formylcytosine (fC), 5-carboxylcytosine (caC), and 5-hydroxymethyluracil (hmU) as putative active demethylation intermediates. Our data suggest that an active oxidative mC demethylation pathway is unlikely to occur. Additionally, we show using HPLC-MS analysis and immunohistochemistry that hmC is present in all tissues and cell types with highest concentrations in neuronal cells of the CNS.Daniel GlobischMartin MünzelMarkus MüllerStylianos MichalakisMirko WagnerSusanne KochTobias BrücklMartin BielThomas CarellPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 12, p e15367 (2010) |
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DOAJ |
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Medicine R Science Q |
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Medicine R Science Q Daniel Globisch Martin Münzel Markus Müller Stylianos Michalakis Mirko Wagner Susanne Koch Tobias Brückl Martin Biel Thomas Carell Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates. |
| description |
5-Hydroxymethylcytosine (hmC) was recently detected as the sixth base in mammalian tissue at so far controversial levels. The function of the modified base is currently unknown, but it is certain that the base is generated from 5-methylcytosine (mC). This fuels the hypothesis that it represents an intermediate of an active demethylation process, which could involve further oxidation of the hydroxymethyl group to a formyl or carboxyl group followed by either deformylation or decarboxylation. Here, we use an ultra-sensitive and accurate isotope based LC-MS method to precisely determine the levels of hmC in various mouse tissues and we searched for 5-formylcytosine (fC), 5-carboxylcytosine (caC), and 5-hydroxymethyluracil (hmU) as putative active demethylation intermediates. Our data suggest that an active oxidative mC demethylation pathway is unlikely to occur. Additionally, we show using HPLC-MS analysis and immunohistochemistry that hmC is present in all tissues and cell types with highest concentrations in neuronal cells of the CNS. |
| format |
article |
| author |
Daniel Globisch Martin Münzel Markus Müller Stylianos Michalakis Mirko Wagner Susanne Koch Tobias Brückl Martin Biel Thomas Carell |
| author_facet |
Daniel Globisch Martin Münzel Markus Müller Stylianos Michalakis Mirko Wagner Susanne Koch Tobias Brückl Martin Biel Thomas Carell |
| author_sort |
Daniel Globisch |
| title |
Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates. |
| title_short |
Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates. |
| title_full |
Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates. |
| title_fullStr |
Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates. |
| title_full_unstemmed |
Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates. |
| title_sort |
tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2010 |
| url |
https://doaj.org/article/72cdefff31ae431fab6f24a71e79a607 |
| work_keys_str_mv |
AT danielglobisch tissuedistributionof5hydroxymethylcytosineandsearchforactivedemethylationintermediates AT martinmunzel tissuedistributionof5hydroxymethylcytosineandsearchforactivedemethylationintermediates AT markusmuller tissuedistributionof5hydroxymethylcytosineandsearchforactivedemethylationintermediates AT stylianosmichalakis tissuedistributionof5hydroxymethylcytosineandsearchforactivedemethylationintermediates AT mirkowagner tissuedistributionof5hydroxymethylcytosineandsearchforactivedemethylationintermediates AT susannekoch tissuedistributionof5hydroxymethylcytosineandsearchforactivedemethylationintermediates AT tobiasbruckl tissuedistributionof5hydroxymethylcytosineandsearchforactivedemethylationintermediates AT martinbiel tissuedistributionof5hydroxymethylcytosineandsearchforactivedemethylationintermediates AT thomascarell tissuedistributionof5hydroxymethylcytosineandsearchforactivedemethylationintermediates |
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1718424048133734400 |