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Genome-wide DNA demethylation in mammals.

Sanz LA, Kota SK, Feil R - Genome Biol. (2010)

Bottom Line: The cytidine deaminase AID and elongator-complex proteins contribute to the extensive removal of DNA methylation in mammalian primordial germ cells and in the paternal pronucleus of the zygote.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Molecular Genetics, CNRS UMR-5535 and University of Montpellier, 1919 route de Mende, Montpellier, France.

ABSTRACT
The cytidine deaminase AID and elongator-complex proteins contribute to the extensive removal of DNA methylation in mammalian primordial germ cells and in the paternal pronucleus of the zygote.

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Related in: MedlinePlus

Active DNA demethylation in mammals. (a) The action of AID on 5-methylcytosine residues (white circles) in DNA (thick black line) gives rise to deaminated 5-methylcytosine, which can be bound by the repair glycosylase MBD4. Through yet-unknown further repair mechanisms, there is conversion into unmethylated cytosines, as shown by the disappearance of the white circles on the lower diagram. The canonical histones found in nucleosomes are colored in blue. In the accessibility model presented here, the presence (green circles) or absence of specific histone tail modifications and/or histone variants (pink spheres) guide the recruitment of the enzymes and other factors involved in the DNA demethylation. It is not yet known whether the requirement for elongator complex proteins is direct or whether they affect DNA demethylation indirectly, by a mechanism unrelated to chromatin. (b) Protection against active DNA demethylation could be linked to the presence of specific histone modifications (red circles). Non-histone proteins could be involved in this process as well.
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Figure 1: Active DNA demethylation in mammals. (a) The action of AID on 5-methylcytosine residues (white circles) in DNA (thick black line) gives rise to deaminated 5-methylcytosine, which can be bound by the repair glycosylase MBD4. Through yet-unknown further repair mechanisms, there is conversion into unmethylated cytosines, as shown by the disappearance of the white circles on the lower diagram. The canonical histones found in nucleosomes are colored in blue. In the accessibility model presented here, the presence (green circles) or absence of specific histone tail modifications and/or histone variants (pink spheres) guide the recruitment of the enzymes and other factors involved in the DNA demethylation. It is not yet known whether the requirement for elongator complex proteins is direct or whether they affect DNA demethylation indirectly, by a mechanism unrelated to chromatin. (b) Protection against active DNA demethylation could be linked to the presence of specific histone modifications (red circles). Non-histone proteins could be involved in this process as well.

Mentions: This novel discovery nicely complements a recent study by Bhutani et al. [3] on heterokaryons made by artificially fusing mouse embryonic stem (ES) cells with human fibroblasts. In these heterokaryons, DNA methylation was rapidly removed from the NANOG and OCT4 genes in the fibroblast-derived genome. By using a small interfering RNA (siRNA) approach, the authors showed that this active demethylation requires AID. Concordantly, AID was found to be targeted specifically to the (methylated) NANOG and OCT4 promoters. In combination, the two new studies demonstrate a novel role for AID in mammals: active demethylation of genomic DNA (Figure 1a).


Genome-wide DNA demethylation in mammals.

Sanz LA, Kota SK, Feil R - Genome Biol. (2010)

Active DNA demethylation in mammals. (a) The action of AID on 5-methylcytosine residues (white circles) in DNA (thick black line) gives rise to deaminated 5-methylcytosine, which can be bound by the repair glycosylase MBD4. Through yet-unknown further repair mechanisms, there is conversion into unmethylated cytosines, as shown by the disappearance of the white circles on the lower diagram. The canonical histones found in nucleosomes are colored in blue. In the accessibility model presented here, the presence (green circles) or absence of specific histone tail modifications and/or histone variants (pink spheres) guide the recruitment of the enzymes and other factors involved in the DNA demethylation. It is not yet known whether the requirement for elongator complex proteins is direct or whether they affect DNA demethylation indirectly, by a mechanism unrelated to chromatin. (b) Protection against active DNA demethylation could be linked to the presence of specific histone modifications (red circles). Non-histone proteins could be involved in this process as well.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2864560&req=5

Figure 1: Active DNA demethylation in mammals. (a) The action of AID on 5-methylcytosine residues (white circles) in DNA (thick black line) gives rise to deaminated 5-methylcytosine, which can be bound by the repair glycosylase MBD4. Through yet-unknown further repair mechanisms, there is conversion into unmethylated cytosines, as shown by the disappearance of the white circles on the lower diagram. The canonical histones found in nucleosomes are colored in blue. In the accessibility model presented here, the presence (green circles) or absence of specific histone tail modifications and/or histone variants (pink spheres) guide the recruitment of the enzymes and other factors involved in the DNA demethylation. It is not yet known whether the requirement for elongator complex proteins is direct or whether they affect DNA demethylation indirectly, by a mechanism unrelated to chromatin. (b) Protection against active DNA demethylation could be linked to the presence of specific histone modifications (red circles). Non-histone proteins could be involved in this process as well.
Mentions: This novel discovery nicely complements a recent study by Bhutani et al. [3] on heterokaryons made by artificially fusing mouse embryonic stem (ES) cells with human fibroblasts. In these heterokaryons, DNA methylation was rapidly removed from the NANOG and OCT4 genes in the fibroblast-derived genome. By using a small interfering RNA (siRNA) approach, the authors showed that this active demethylation requires AID. Concordantly, AID was found to be targeted specifically to the (methylated) NANOG and OCT4 promoters. In combination, the two new studies demonstrate a novel role for AID in mammals: active demethylation of genomic DNA (Figure 1a).

Bottom Line: The cytidine deaminase AID and elongator-complex proteins contribute to the extensive removal of DNA methylation in mammalian primordial germ cells and in the paternal pronucleus of the zygote.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Molecular Genetics, CNRS UMR-5535 and University of Montpellier, 1919 route de Mende, Montpellier, France.

ABSTRACT
The cytidine deaminase AID and elongator-complex proteins contribute to the extensive removal of DNA methylation in mammalian primordial germ cells and in the paternal pronucleus of the zygote.

Show MeSH
Related in: MedlinePlus