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Mammalian Non-CpG Methylation: Stem Cells and Beyond

1
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA
2
Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, 3515 Civic Center Boulevard, Philadelphia, PA 19104, USA 
Biology 2014, 3(4), 739-751; https://doi.org/10.3390/biology3040739
Received: 9 June 2014 / Revised: 4 November 2014 / Accepted: 5 November 2014 / Published: 11 November 2014
(This article belongs to the Special Issue DNA Methylation)
Although CpG dinucleotides remain the primary site for DNA methylation in mammals, there is emerging evidence that DNA methylation at non-CpG sites (CpA, CpT and CpC) is not only present in mammalian cells, but may play a unique role in the regulation of gene expression. For some time it has been known that non-CpG methylation is abundant in plants and present in mammalian embryonic stem cells, but non-CpG methylation was thought to be lost upon cell differentiation. However, recent publications have described a role for non-CpG methylation in adult mammalian somatic cells including the adult mammalian brain, skeletal muscle, and hematopoietic cells and new interest in this field has been stimulated by the availability of high throughput sequencing techniques that can accurately measure this epigenetic modification. Genome wide assays indicate that non-CpG methylation is negligible in human fetal brain, but abundant in human adult brain tissue. Genome wide measurement of non-CpG methylation coupled with RNA-Sequencing indicates that in the human adult brain non-CpG methylation levels are inversely proportional to the abundance of mRNA transcript at the associated gene. Additionally specific examples where alterations in non-CpG methylation lead to changes in gene expression have been described; in PGC1α in human skeletal muscle, IFN-γ in human T-cells and SYT11 in human brain, all of which contribute to the development of human disease. View Full-Text
Keywords: non-CpG methylation; epigenetics; bisulfite sequencing; MeDIP; RRBS1 non-CpG methylation; epigenetics; bisulfite sequencing; MeDIP; RRBS1
MDPI and ACS Style

Pinney, S.E. Mammalian Non-CpG Methylation: Stem Cells and Beyond. Biology 2014, 3, 739-751.

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