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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.


Modified DNA bases and their functions.
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Fig3: Modified DNA bases and their functions.

Mentions: Epigenetic DNA modifications generally affect the accessibility of genomic regions for regulatory proteins or protein complexes, for example by preventing interactions or by recruiting specific readers. Consequently, this can influence the chromatin structure and/or directly regulate enhancer and promoter activity or transcriptional processivity. Cytosine methylation is so far the only known symmetric modification with an established maintenance mechanism, which represents a unique feature that currently distinguishes 5mC from all other epigenetic modifications. 5mC has mostly been related to gene repression, in particular at enhancer and promoter regions of genes (Figure 3), but might also play an important role in positively influencing transcription, either by recruiting methylation-specific transcription factors [82, 83] or by a yet to be understood mechanism when present in the body of active genes [35].Figure 3


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

Breiling A, Lyko F - Epigenetics Chromatin (2015)

Modified DNA bases and their functions.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig3: Modified DNA bases and their functions.
Mentions: Epigenetic DNA modifications generally affect the accessibility of genomic regions for regulatory proteins or protein complexes, for example by preventing interactions or by recruiting specific readers. Consequently, this can influence the chromatin structure and/or directly regulate enhancer and promoter activity or transcriptional processivity. Cytosine methylation is so far the only known symmetric modification with an established maintenance mechanism, which represents a unique feature that currently distinguishes 5mC from all other epigenetic modifications. 5mC has mostly been related to gene repression, in particular at enhancer and promoter regions of genes (Figure 3), but might also play an important role in positively influencing transcription, either by recruiting methylation-specific transcription factors [82, 83] or by a yet to be understood mechanism when present in the body of active genes [35].Figure 3

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.