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Transient Accumulation of 5-Carboxylcytosine Indicates Involvement of Active Demethylation in Lineage Specification of Neural Stem Cells

Wheldon, Lee M.; Abakir, Abdulkadir; Ferjentsik, Zoltan; Dudnakova, Tatiana; Strohbuecker, Stephanie; Christie, Denise; Dai, Nan; Guan, Shengxi; Foster, Jeremy M.; Corrêa, Ivan R.; Loose, Matthew; Dixon, James E.; Sottile, Virginie; Johnson, Andrew D.; Ruzov, Alexey

Authors

Lee M. Wheldon Lee.Wheldon@nottingham.ac.uk

Abdulkadir Abakir

Zoltan Ferjentsik

Tatiana Dudnakova

Stephanie Strohbuecker

Denise Christie Denise.Mclean@nottingham.ac.uk

Nan Dai

Shengxi Guan

Jeremy M. Foster

Ivan R. Corrêa

Matthew Loose

James E. Dixon

Virginie Sottile

Andrew D. Johnson

Alexey Ruzov



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.

Journal Article Type Article
Publication Date Jun 12, 2014
Journal Cell Reports
Print ISSN 2211-1247
Electronic ISSN 2211-1247
Publisher Elsevier (Cell Press)
Peer Reviewed Peer Reviewed
Volume 7
Issue 5
Pages 1353-1361
APA6 Citation Wheldon, L. M., Abakir, A., Ferjentsik, Z., Dudnakova, T., Strohbuecker, S., Christie, D., …Ruzov, A. (2014). Transient Accumulation of 5-Carboxylcytosine Indicates Involvement of Active Demethylation in Lineage Specification of Neural Stem Cells. Cell Reports, 7(5), 1353-1361. https://doi.org/10.1016/j.celrep.2014.05.003
DOI https://doi.org/10.1016/j.celrep.2014.05.003
Publisher URL http://www.cell.com/cell-reports/abstract/S2211-1247(14)00378-7
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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