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Epigenetic regulatory functions of DNA modifications: 5-methylcytosine and beyond.

Breiling A, Lyko F - Epigenetics Chromatin (2015)

Bottom Line: Furthermore, the discovery of enzymes that catalyse the hydroxylation of 5-methylcytosine to 5-hydroxymethylcytosine not only identified an active demethylation pathway, but also a candidate for a new epigenetic mark associated with activated transcription.Most recently, N6-methyladenine was described as an additional eukaryotic DNA modification with epigenetic regulatory potential.This newfound diversity of DNA modifications and their potential for combinatorial interactions indicates that the epigenetic DNA code is substantially more complex than previously thought.

View Article: PubMed Central - PubMed

Affiliation: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.

ABSTRACT
The chemical modification of DNA bases plays a key role in epigenetic gene regulation. While much attention has been focused on the classical epigenetic mark, 5-methylcytosine, the field garnered increased interest through the recent discovery of additional modifications. In this review, we focus on the epigenetic regulatory roles of DNA modifications in animals. We present the symmetric modification of 5-methylcytosine on CpG dinucleotide as a key feature, because it permits the inheritance of methylation patterns through DNA replication. However, the distribution patterns of cytosine methylation are not conserved in animals and independent molecular functions will likely be identified. Furthermore, the discovery of enzymes that catalyse the hydroxylation of 5-methylcytosine to 5-hydroxymethylcytosine not only identified an active demethylation pathway, but also a candidate for a new epigenetic mark associated with activated transcription. Most recently, N6-methyladenine was described as an additional eukaryotic DNA modification with epigenetic regulatory potential. Interestingly, this modification is also present in genomes that lack canonical cytosine methylation patterns, suggesting independent functions. This newfound diversity of DNA modifications and their potential for combinatorial interactions indicates that the epigenetic DNA code is substantially more complex than previously thought.

No MeSH data available.


Three major categories of animal methylomes. Ubiquitous, sporadic and absent DNA methylation (5mC) are illustrated with three examples from whole-genome bisulfite sequencing analyses of mouse (top), honey bee (middle) and Drosophila DNA (bottom). Methylation ratios for each CpG dinucleotide in a randomly selected 40 kB window are shown. Gene features are indicated below each panel. Transparent blue bars indicate the range of bisulfite conversion artifacts (methylation ratios below 0.2).
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Fig2: Three major categories of animal methylomes. Ubiquitous, sporadic and absent DNA methylation (5mC) are illustrated with three examples from whole-genome bisulfite sequencing analyses of mouse (top), honey bee (middle) and Drosophila DNA (bottom). Methylation ratios for each CpG dinucleotide in a randomly selected 40 kB window are shown. Gene features are indicated below each panel. Transparent blue bars indicate the range of bisulfite conversion artifacts (methylation ratios below 0.2).

Mentions: Beyond mammalian methylomes, the comparative analysis of single-base resolution methylation maps has shown a substantial degree of variation between animal species [15, 20, 21]. The available information can be used to define three major categories (Figure 2): the first group is defined by mammalian methylomes and is characterized by pervasive methylation. In the human genome, more than 80% of the CpG dinucleotides are methylated, creating a landscape of ubiquitous methylation, but with local gaps that are often found at active regulatory elements, such as promoters and enhancers (Figure 2). It seems plausible to assume that the default state of these methylomes is “methylated” and that active mechanisms (see below) are required to keep specific regions free of methylation.Figure 2


Epigenetic regulatory functions of DNA modifications: 5-methylcytosine and beyond.

Breiling A, Lyko F - Epigenetics Chromatin (2015)

Three major categories of animal methylomes. Ubiquitous, sporadic and absent DNA methylation (5mC) are illustrated with three examples from whole-genome bisulfite sequencing analyses of mouse (top), honey bee (middle) and Drosophila DNA (bottom). Methylation ratios for each CpG dinucleotide in a randomly selected 40 kB window are shown. Gene features are indicated below each panel. Transparent blue bars indicate the range of bisulfite conversion artifacts (methylation ratios below 0.2).
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC4507326&req=5

Fig2: Three major categories of animal methylomes. Ubiquitous, sporadic and absent DNA methylation (5mC) are illustrated with three examples from whole-genome bisulfite sequencing analyses of mouse (top), honey bee (middle) and Drosophila DNA (bottom). Methylation ratios for each CpG dinucleotide in a randomly selected 40 kB window are shown. Gene features are indicated below each panel. Transparent blue bars indicate the range of bisulfite conversion artifacts (methylation ratios below 0.2).
Mentions: Beyond mammalian methylomes, the comparative analysis of single-base resolution methylation maps has shown a substantial degree of variation between animal species [15, 20, 21]. The available information can be used to define three major categories (Figure 2): the first group is defined by mammalian methylomes and is characterized by pervasive methylation. In the human genome, more than 80% of the CpG dinucleotides are methylated, creating a landscape of ubiquitous methylation, but with local gaps that are often found at active regulatory elements, such as promoters and enhancers (Figure 2). It seems plausible to assume that the default state of these methylomes is “methylated” and that active mechanisms (see below) are required to keep specific regions free of methylation.Figure 2

Bottom Line: Furthermore, the discovery of enzymes that catalyse the hydroxylation of 5-methylcytosine to 5-hydroxymethylcytosine not only identified an active demethylation pathway, but also a candidate for a new epigenetic mark associated with activated transcription.Most recently, N6-methyladenine was described as an additional eukaryotic DNA modification with epigenetic regulatory potential.This newfound diversity of DNA modifications and their potential for combinatorial interactions indicates that the epigenetic DNA code is substantially more complex than previously thought.

View Article: PubMed Central - PubMed

Affiliation: Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.

ABSTRACT
The chemical modification of DNA bases plays a key role in epigenetic gene regulation. While much attention has been focused on the classical epigenetic mark, 5-methylcytosine, the field garnered increased interest through the recent discovery of additional modifications. In this review, we focus on the epigenetic regulatory roles of DNA modifications in animals. We present the symmetric modification of 5-methylcytosine on CpG dinucleotide as a key feature, because it permits the inheritance of methylation patterns through DNA replication. However, the distribution patterns of cytosine methylation are not conserved in animals and independent molecular functions will likely be identified. Furthermore, the discovery of enzymes that catalyse the hydroxylation of 5-methylcytosine to 5-hydroxymethylcytosine not only identified an active demethylation pathway, but also a candidate for a new epigenetic mark associated with activated transcription. Most recently, N6-methyladenine was described as an additional eukaryotic DNA modification with epigenetic regulatory potential. Interestingly, this modification is also present in genomes that lack canonical cytosine methylation patterns, suggesting independent functions. This newfound diversity of DNA modifications and their potential for combinatorial interactions indicates that the epigenetic DNA code is substantially more complex than previously thought.

No MeSH data available.