| Literature DB >> 24882006 |
Lee M Wheldon1, Abdulkadir Abakir2, Zoltan Ferjentsik3, Tatiana Dudnakova4, Stephanie Strohbuecker2, Denise Christie3, Nan Dai5, Shengxi Guan5, Jeremy M Foster5, Ivan R Corrêa5, Matthew Loose3, James E Dixon2, Virginie Sottile6, Andrew D Johnson3, Alexey Ruzov7.
Abstract
5-Methylcytosine (5mC) is an epigenetic modification involved in regulation of gene activity during differentiation. Tet dioxygenases oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Both 5fC and 5caC can be excised from DNA by thymine-DNA glycosylase (TDG) followed by regeneration of unmodified cytosine via the base excision repair pathway. Despite evidence that this mechanism is operative in embryonic stem cells, the role of TDG-dependent demethylation in differentiation and development is currently unclear. Here, we demonstrate that widespread oxidation of 5hmC to 5caC occurs in postimplantation mouse embryos. We show that 5fC and 5caC are transiently accumulated during lineage specification of neural stem cells (NSCs) in culture and in vivo. Moreover, 5caC is enriched at the cell-type-specific promoters during differentiation of NSCs, and TDG knockdown leads to increased 5fC/5caC levels in differentiating NSCs. Our data suggest that active demethylation contributes to epigenetic reprogramming determining lineage specification in embryonic brain.Entities:
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Year: 2014 PMID： 24882006 DOI： 10.1016/j.celrep.2014.05.003
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423