Local chromatin microenvironment determines DNMT activity: from DNA methyltransferase to DNA demethylase or DNA dehydroxymethylase

Wijst, Monique G. P. van der; Muralidhar, Venkiteswaran; Chen, Hui; Xu, Guoliang; Plösch, Torsten; Rots, Marianne G.

doi:10.1080/15592294.2015.1062204

Cited by 74 publications

(65 citation statements)

References 58 publications

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“…DNMT1, which is abundant also in the adult CNS, ensures that the hemimethylated DNA strand is maintained during DNA replication and thus the methylation status is passed on. In addition, DNMT1 may act as dehydroxymethylase under conditions of oxidative stress and in the absence of SAM and high intracellular calcium levels Van der Wijst et al 2015). The de novo DNMT3a and 3b are capable to methylate unmethylated DNA.…”

Section: Dna Methylationmentioning

confidence: 99%

DNA methylation in Parkinson's disease

Wüllner

Kaut

deBoni

et al. 2016

Journal of Neurochemistry

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Epigenetic processes control the embryonic development into multicellular organisms and determine the functional differences of genetically identical cells and individuals. They are also involved in a variety of complex functions such as learning and memory consolidation and have been implicated in aging processes. Beyond the actual genetic information encoded in the DNA sequence, epigenetic modifications in particular DNA methylation and various histone modifications shape the chromatin into a transcriptional permissive or repressive state. DNA methylation patterns are altered by environmental conditions and can be carried forward through mitosis and meiosis. Hence, DNA methylation probably mediates complex environment-gene interactions, determines individual disease characteristics, and contributes to effects and side effects of drugs. In addition to classic monogenic epigenetic diseases, i.e., Prader-Willi and Rett syndrome, recent data point to an epigenetic component also in apparent sporadic neuro-psychiatric disorders and increasing evidence suggests a role for altered DNA methylation in Parkinson's disease. Epigenetic alterations, DNA methylation in particular, may account for the yet unexplained individual susceptibility and the variability in the course of Parkinson's disease and could provide hints toward the development of novel therapeutic targets.

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Section: Dna Methylationmentioning

confidence: 99%

DNA methylation in Parkinson's disease

Wüllner

Kaut

deBoni

et al. 2016

Journal of Neurochemistry

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“…H3K4me3 requires the presence of H3K79me in order to be stabilized and successfully maintained. Based on these, and other findings [87], it might turn out that the chromatin microenvironment greatly affects the outcome of epigenetic reprogramming.…”

Section: Next Stage Of Epigenetic Editing: Sustained Epigenetic Repromentioning

confidence: 67%

Epigenetic Editing: On the Verge of Reprogramming Gene Expression at Will

Cano-Rodríguez

Rots

2016

Curr Genet Med Rep

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Genome targeting has quickly developed as one of the most promising fields in science. By using programmable DNA-binding platforms and nucleases, scientists are now able to accurately edit the genome. These DNA-binding tools have recently also been applied to engineer the epigenome for gene expression modulation. Such epigenetic editing constructs have firmly demonstrated the causal role of epigenetics in instructing gene expression. Another focus of epigenome engineering is to understand the order of events of chromatin remodeling in gene expression regulation. Groundbreaking approaches in this field are beginning to yield novel insights into the function of individual chromatin marks in the context of maintaining cellular phenotype and regulating transient gene expression changes. This review focuses on recent advances in the field of epigenetic editing and highlights its promise for sustained gene expression reprogramming.

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“…and is usually preceded by repressive H3K9 methylation marks. Interestingly, in the case of very low availability of methyl donor, DNMT3A/B cannot methylate CpGs, but in contrast have been reported to actively participate in DNA demethylation [15].…”

Section: Dna Methyltransferases (Dnmts)mentioning

confidence: 99%

Chromatin-remodeling enzymes in control of Schwann cell development, maintenance and plasticity

Jacob

2017

Current Opinion in Neurobiology

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Gene regulation is essential for cellular differentiation and plasticity. Schwann cells (SCs), the myelinating glia of the peripheral nervous system (PNS), develop from neural crest cells to mature myelinating SCs and can at early developmental stage differentiate into various cell types. After a PNS lesion, SCs can also convert into repair cells that guide and stimulate axonal regrowth, and remyelinate regenerated axons. What controls their development and versatile nature? Several recent studies highlight the key roles of chromatin modifiers in these processes, allowing SCs to regulate their gene expression profile and thereby acquire or change their identity and quickly react to their environment. AddressDepartment of Biology, University of Fribourg, Chemin du Musé e 10, 1700 Fribourg, SwitzerlandCorresponding author: Jacob, Claire (claire.jacob@unifr.ch) IntroductionSCs originate from neural crest cells that also give rise to other cell types including sensory neurons, chondrocytes, melanocytes, smooth-muscle cells [1,2]. After specification in SC precursors, the lineage further differentiates into immature SCs that encircle bundles of axons of different calibers. Next, big caliber axons are sorted in a one-to-one relationship with SCs by a process called radial sorting which leads to the promyelinating stage. The last step of maturation is the myelination process where SCs build a thick myelin sheath rich in lipids around axons (Figure 1). Meanwhile, small caliber axons remain in bundles associated with non-myelinating SCs and persist as Remak bundles in adult nerves [3,4]. Myelin provides axonal insulation and fast conduction of electric signals along axons; its formation and maintenance are thus critical for neuronal functions. By contrast, myelin is detrimental for axonal regrowth after lesion, because it contains growth inhibitory proteins [5]. However, SCs react quickly to an axonal lesion by dedifferentiating, digesting their own myelin -a process called myelinophagy [6] -and converting into repair cells [7,8] that foster axonal regrowth and guide axons back to their former target [9,10]. SCs then remyelinate regenerated axons (Figure 2). This remarkable SC plasticity allows the PNS to functionally regenerate after lesion.This review is focused on the mechanisms of SC development, maintenance and plasticity after lesion controlled by chromatin-remodeling enzymes. Chromatin remodeling regulates the accessibility of genes for the transcriptional machinery, and thereby gene activation and repression. Changes of chromatin architecture are controlled by ATP-dependent nucleosome remodeling and by covalent modifications, either on DNA by methylation or on histones by various post-translational modifications including acetylation, methylation, phosphorylation, ubiquitination, SUMOylation, ADP-ribosylation. Although our knowledge on these mechanisms is still very sparse, recent findings on the functions of chromatinremodeling enzymes have significantly contributed to a better understanding of their critical fu...

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Local chromatin microenvironment determines DNMT activity: from DNA methyltransferase to DNA demethylase or DNA dehydroxymethylase

Abstract: These authors contributed equally to this work.

Cited by 74 publications

References 58 publications

DNA methylation in Parkinson's disease

DNA methylation in Parkinson's disease

Epigenetic Editing: On the Verge of Reprogramming Gene Expression at Will

Chromatin-remodeling enzymes in control of Schwann cell development, maintenance and plasticity

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