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Biology 2014, 3(4), 670-723; doi:10.3390/biology3040670

DNA Modifications: Function and Applications in Normal and Disease States

1
Department of Biochemistry and Medical Genetics, Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada
2
Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB R3E 0J9, Canada
3
Department of Pathology, University of Manitoba, Winnipeg, MB R3E 3P5, Canada
These authors contributed equally to this paper.
*
Author to whom correspondence should be addressed.
Received: 15 July 2014 / Revised: 22 September 2014 / Accepted: 24 September 2014 / Published: 22 October 2014
(This article belongs to the Special Issue DNA Methylation)
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Abstract

Epigenetics refers to a variety of processes that have heritable effects on gene expression programs without changes in DNA sequence. Key players in epigenetic control are chemical modifications to DNA, histone, and non-histone chromosomal proteins, which establish a complex regulatory network that controls genome function. Methylation of DNA at the fifth position of cytosine in CpG dinucleotides (5-methylcytosine, 5mC), which is carried out by DNA methyltransferases, is commonly associated with gene silencing. However, high resolution mapping of DNA methylation has revealed that 5mC is enriched in exonic nucleosomes and at intron-exon junctions, suggesting a role of DNA methylation in the relationship between elongation and RNA splicing. Recent studies have increased our knowledge of another modification of DNA, 5-hydroxymethylcytosine (5hmC), which is a product of the ten-eleven translocation (TET) proteins converting 5mC to 5hmC. In this review, we will highlight current studies on the role of 5mC and 5hmC in regulating gene expression (using some aspects of brain development as examples). Further the roles of these modifications in detection of pathological states (type 2 diabetes, Rett syndrome, fetal alcohol spectrum disorders and teratogen exposure) will be discussed. View Full-Text
Keywords: DNA methylation; 5-methylcytosine; 5-hydroxymethylcytosine; methyl binding proteins; teratogens; brain development; neurological disorders; biomarkers; diabetes DNA methylation; 5-methylcytosine; 5-hydroxymethylcytosine; methyl binding proteins; teratogens; brain development; neurological disorders; biomarkers; diabetes
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Liyanage, V.R.B.; Jarmasz, J.S.; Murugeshan, N.; Del Bigio, M.R.; Rastegar, M.; Davie, J.R. DNA Modifications: Function and Applications in Normal and Disease States. Biology 2014, 3, 670-723.

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