1,027
Views
25
CrossRef citations to date
0
Altmetric
Point of View

Mammalian DNA demethylation

Multiple faces and upstream regulation

Pages 679-684 | Received 03 Apr 2013, Accepted 08 May 2013, Published online: 17 May 2013

Figures & data

Figure 1. The multiple faces of mammalian DNA demethylation. Schematic representation of the enzymology implicated in 5-methylcytosine (5mC) demethylation. The exocyclic group at carbon 5 of each cytosine derivative is highlighted in red. C, cytosine; T, thymine; 5hmC, 5-hydroxymethylcytosine; 5fC, 5-formylcytosine; 5caC, 5-carboxylcytosine; BER: base excision repair; NER, nucleotide excision repair. Note: Direct base excision repair of 5mC and potential deamination of 5hmC to 5-hydroxymethyluracil has not been considered due to lack of experimental confirmation. For details see main text.

Figure 1. The multiple faces of mammalian DNA demethylation. Schematic representation of the enzymology implicated in 5-methylcytosine (5mC) demethylation. The exocyclic group at carbon 5 of each cytosine derivative is highlighted in red. C, cytosine; T, thymine; 5hmC, 5-hydroxymethylcytosine; 5fC, 5-formylcytosine; 5caC, 5-carboxylcytosine; BER: base excision repair; NER, nucleotide excision repair. Note: Direct base excision repair of 5mC and potential deamination of 5hmC to 5-hydroxymethyluracil has not been considered due to lack of experimental confirmation. For details see main text.

Figure 2. Ing1 directs Gadd45a and the demethylation machinery to H3K4me3. Proposed model for site-specific demethylation by Gadd45a. At a given gene promoter histone H3 trimethylated at lysine 4 (H3K4me3) is specifically recognized by Ing1. Gadd45a and the repair machinery are recruited through Ing1 binding. Subsequently, 5mCs are excised by DNA repair leading to DNA demethylation. Additional targeting factors may be required for the process. G45a, Gadd45a; NER, nucleotide excision repair; BER, base excision repair. Figure is from ref. Citation67 with permission of the authors.

Figure 2. Ing1 directs Gadd45a and the demethylation machinery to H3K4me3. Proposed model for site-specific demethylation by Gadd45a. At a given gene promoter histone H3 trimethylated at lysine 4 (H3K4me3) is specifically recognized by Ing1. Gadd45a and the repair machinery are recruited through Ing1 binding. Subsequently, 5mCs are excised by DNA repair leading to DNA demethylation. Additional targeting factors may be required for the process. G45a, Gadd45a; NER, nucleotide excision repair; BER, base excision repair. Figure is from ref. Citation67 with permission of the authors.