Mammalian Non-CpG Methylation: Stem Cells and Beyond

Pinney, Sara E.

doi:10.3390/biology3040739

Cited by 69 publications

(44 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this procedure, regulatory information in the form of an epigenetic chemical modification is thus converted to a genetic sequence variant, which can be captured by standard sequencing technologies or other assay methods. Several characteristics of mCH make reliable detection difficult (74). First, mCH is not present in most somatic cells, and only limited types of cells have been found to contain mCH (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Non-CG Methylation in the Human Genome

Ecker

2015

Annu. Rev. Genom. Hum. Genet.

217

213

View full text Add to dashboard Cite

DNA methylation is a chemical modification that occurs predominantly on CG dinucleotides in mammalian genomes. However, recent studies have revealed that non-CG methylation (mCH) is abundant and nonrandomly distributed in the genomes of pluripotent cells and brain cells, and is present at lower levels in many other human cells and tissues. Surprisingly, mCH in pluripotent cells is distinct from that in brain cells in terms of sequence specificity and association with transcription, indicating the existence of different mCH pathways. In addition, several recent studies have begun to reveal the biological significance of mCH in diverse cellular processes. In reprogrammed somatic cells, mCH marks megabase-scale regions that have failed to revert to the pluripotent epigenetic state. In myocytes, promoter mCH accumulation is associated with the transcriptional response to environmental factors. In brain cells, mCH accumulates during the establishment of neural circuits and is associated with Rett syndrome. In this review, we summarize the current understanding of mCH and its possible functional consequences in different biological contexts.

show abstract

Section: Introductionmentioning

confidence: 99%

Non-CG Methylation in the Human Genome

Ecker

2015

Annu. Rev. Genom. Hum. Genet.

217

213

View full text Add to dashboard Cite

show abstract

“…Recently, a role for MeCP2 binding to CpH sites and regulating the expression of genes enriched for neuronal function has been described (Chen et al ). Non‐CpG methylation has been reported in vertebrate neurons (Fatemi & Wade ; Guo et al ; Pinney ) and in Drosophila ; the methylation present in the adult genome is enriched on non‐CpG motifs, particularly CpT and CpA dinucleotides (Boffelli et al ; Capuano et al ; Takayama et al ). In our sleep experiments, MeCP2 may be functioning to translate endogenous CpH methylation into changes in gene expression.…”

Section: Discussionmentioning

confidence: 99%

Functional conservation of MBD proteins: MeCP2 and Drosophila MBD proteins alter sleep

Gupta¹,

Morgan

Bailey

et al. 2016

Genes Brain and Behavior

View full text Add to dashboard Cite

Proteins containing a methyl-CpG-binding domain (MBD) bind 5mC and convert the methylation pattern information into appropriate functional cellular states. The correct readout of epigenetic marks is of particular importance in the nervous system where abnormal expression or compromised MBD protein function, can lead to disease and developmental disorders. Recent evidence indicates the genome of Drosophila melanogaster is methylated and two MBD proteins, dMBD2/3 and dMBD-R2, are present. Are Drosophila MBD proteins required for neuronal function, and as MBD-containing proteins have diverged and evolved, does the MBD domain retain the molecular properties required for conserved cellular function across species? To address these questions, we expressed the human MBD-containing protein, hMeCP2, in distinct amine neurons and quantified functional changes in sleep circuitry output using a high throughput assay in Drosophila. hMeCP2 expression resulted in phase-specific sleep loss and sleep fragmentation with the hMeCP2-mediated sleep deficits requiring an intact MBD-domain. Reducing endogenous dMBD2/3 and dMBD-R2 levels also generated sleep fragmentation, with an increase in sleep occurring upon dMBD-R2 reduction. To examine if hMeCP2 and dMBD-R2 are targeting common neuronal functions, we reduced dMBD-R2 levels in combination with hMeCP2 expression and observed a complete rescue of sleep deficits. Furthermore, chromosomal binding experiments indicate MBD-R2 and MeCP2 associate on shared genomic loci. Our results provide the first demonstration that Drosophila MBD-containing family members are required for neuronal function and suggest the MBD domain retains considerable functional conservation at the whole organism level across species.

show abstract

“…In mammalian differentiated cells this modification mainly occurs in a CpG dinucleotide (Bird 2011). However, non-CpG methylation has also been reported in embryonic stem cells; although its function is not fully understood, it seems to play a role in pluripotency, and when present in promoters can regulate the expression of some genes (Ramsahoye, Biniszkiewicz et al 2000, Patil, Ward et al 2014, Pinney 2014. DNA methylation is not randomly spread throughout the genome.…”

Section: Dna Methylationmentioning

confidence: 99%

Does epigenetic dysregulation of pancreatic islets contribute to impaired insulin secretion and type 2 diabetes?

Dayeh

Ling

2015

Biochem. Cell Biol.

View full text Add to dashboard Cite

β cell dysfunction is central to the development and progression of type 2 diabetes (T2D). T2D develops when β cells are not able to compensate for the increasing demand for insulin caused by insulin resistance. Epigenetic modifications play an important role in establishing and maintaining β cell identity and function in physiological conditions. On the other hand, epigenetic dysregulation can cause a loss of β cell identity, which is characterized by reduced expression of genes that are important for β cell function, ectopic expression of genes that are not supposed to be expressed in β cells, and loss of genetic imprinting. Consequently, this may lead to β cell dysfunction and impaired insulin secretion. Risk factors that can cause epigenetic dysregulation include parental obesity, an adverse intrauterine environment, hyperglycemia, lipotoxicity, aging, physical inactivity, and mitochondrial dysfunction. These risk factors can affect the epigenome at different time points throughout the lifetime of an individual and even before an individual is conceived. The plasticity of the epigenome enables it to change in response to environmental factors such as diet and exercise, and also makes the epigenome a good target for epigenetic drugs that may be used to enhance insulin secretion and potentially treat diabetes.

show abstract

Mammalian Non-CpG Methylation: Stem Cells and Beyond

Cited by 69 publications

References 46 publications

Non-CG Methylation in the Human Genome

Non-CG Methylation in the Human Genome

Functional conservation of MBD proteins: MeCP2 and Drosophila MBD proteins alter sleep

Does epigenetic dysregulation of pancreatic islets contribute to impaired insulin secretion and type 2 diabetes?

Contact Info

Product

Resources

About