Epigenetic Basis of Regeneration: Analysis of Genomic DNA Methylation Profiles in the MRL/MpJ Mouse

Górnikiewicz, Bartosz; Ronowicz, Anna; Podolak, Justyna; Madanecki, Piotr; Stanisławska-Sachadyn, Anna; Sachadyn, Paweł

doi:10.1093/dnares/dst034

Cited by 19 publications

(7 citation statements)

References 48 publications

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“…Methylated DNA immunoprecipitation (MeDIP) followed by microarray analysis was performed for tissue pools collected from three individuals at d1, d7, w2 and w8. MeDIP, labelling, hybridization and image acquisition were performed as previously described [ 27 ] using Mouse DNA Methylation 3x720K CpG Island Plus RefSeq Promoter Arrays (Roche, NimbleGen).…”

Section: Methodsmentioning

confidence: 99%

Changes in gene methylation patterns in neonatal murine hearts: Implications for the regenerative potential

et al. 2016

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BackgroundThe neonatal murine heart is able to regenerate after severe injury; this capacity however, quickly diminishes and it is lost within the first week of life. DNA methylation is an epigenetic mechanism which plays a crucial role in development and gene expression regulation. Under investigation here are the changes in DNA methylation and gene expression patterns which accompany the loss of regenerative potential.ResultsThe MeDIP-chip (methylated DNA immunoprecipitation microarray) approach was used in order to compare global DNA methylation profiles in whole murine hearts at day 1, 7, 14 and 56 complemented with microarray transcriptome profiling. We found that the methylome transition from day 1 to day 7 is characterized by the excess of genomic regions which gain over those that lose DNA methylation. A number of these changes were retained until adulthood. The promoter genomic regions exhibiting increased DNA methylation at day 7 as compared to day 1 are significantly enriched in the genes critical for heart maturation and muscle development. Also, the promoter genomic regions showing an increase in DNA methylation at day 7 relative to day 1 are significantly enriched with a number of transcription factors binding motifs including those of Mfsd6l, Mef2c, Meis3, Tead4, and Runx1.ConclusionsThe results indicate that the extensive alterations in DNA methylation patterns along the development of neonatal murine hearts are likely to contribute to the decline of regenerative capabilities observed shortly after birth. This conclusion is supported by the evidence that an increase in DNA methylation in the neonatal murine heart from day 1 to day 7 occurs in the promoter regions of genes playing important roles in cardiovascular system development.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2545-1) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Changes in gene methylation patterns in neonatal murine hearts: Implications for the regenerative potential

et al. 2016

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“…Epigenetic regulation has an essential role in cell differentiation, which is a characteristic process involved in plant regeneration. DNA methylation has been reported as one of the most important factors in phenotypic changes and is considered as one of the most important epigenetic mechanisms that play a role in the plant regeneration process [ 162 , 163 ]. Obtaining true-to-type plants is the main target of large-scale clonal multiplication.…”

Section: Molecular Basis Of Plant Regenerationmentioning

confidence: 99%

Cellular, Molecular, and Physiological Aspects of In Vitro Plant Regeneration

Bidabadi

Jain

2020

Plants

146

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Plants generally have the highest regenerative ability because they show a high degree of developmental plasticity. Although the basic principles of plant regeneration date back many years, understanding the cellular, molecular, and physiological mechanisms based on these principles is currently in progress. In addition to the significant effects of some factors such as medium components, phytohormones, explant type, and light on the regeneration ability of an explant, recent reports evidence the involvement of molecular signals in organogenesis and embryogenesis responses to explant wounding, induced plant cell death, and phytohormones interaction. However, some cellular behaviors such as the occurrence of somaclonal variations and abnormalities during the in vitro plant regeneration process may be associated with adverse effects on the efficacy of plant regeneration. A review of past studies suggests that, in some cases, regeneration in plants involves the reprogramming of distinct somatic cells, while in others, it is induced by the activation of relatively undifferentiated cells in somatic tissues. However, this review covers the most important factors involved in the process of plant regeneration and discusses the mechanisms by which plants monitor this process.

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“…As the decline in regenerative capacity with development is likely to be linked to epigenetic repression [1,[5], [6], [7],28,29], the question arises as to whether epigenetic inhibitors can restore this lost ability. Epigenetic derepression alone may be insufficient to activate silenced genes without positive induction.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic inhibitor zebularine activates ear pinna wound closure in the mouse

et al. 2019

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Background Most studies on regenerative medicine focus on cell-based therapies and transplantations. Small-molecule therapeutics, though proved effective in different medical conditions, have not been extensively investigated in regenerative research. It is known that healing potential decreases with development and developmental changes are driven by epigenetic mechanisms, which suggests epigenetic repression of regenerative capacity. Methods We applied zebularine, a nucleoside inhibitor of DNA methyltransferases, to stimulate the regenerative response in a model of ear pinna injury in mice. Findings We observed the regeneration of complex tissue that was manifested as improved ear hole repair in mice that received intraperitoneal injections of zebularine. Six weeks after injury, the mean hole area decreased by 83.2 ± 9.4% in zebularine-treated and by 43.6 ± 15.4% in control mice (p < 10 −30 ). Combined delivery of zebularine and retinoic acid potentiated and accelerated this effect, resulting in complete ear hole closure within three weeks after injury. We found a decrease in DNA methylation and transcriptional activation of neurodevelopmental and pluripotency genes in the regenerating tissues. Interpretation This study is the first to demonstrate an effective induction of complex tissue regeneration in adult mammals using zebularine. We showed that the synergistic action of an epigenetic drug (zebularine) and a transcriptional activator (retinoic acid) could be effectively utilized to induce the regenerative response, thus delineating a novel pharmacological strategy for regeneration. The strategy was effective in the model of ear pinna regeneration in mice, but zebularine acts on different cell types, therefore, a similar approach can be tested in other tissues and organs.

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Epigenetic Basis of Regeneration: Analysis of Genomic DNA Methylation Profiles in the MRL/MpJ Mouse

Cited by 19 publications

References 48 publications

Changes in gene methylation patterns in neonatal murine hearts: Implications for the regenerative potential

Changes in gene methylation patterns in neonatal murine hearts: Implications for the regenerative potential

Cellular, Molecular, and Physiological Aspects of In Vitro Plant Regeneration

Epigenetic inhibitor zebularine activates ear pinna wound closure in the mouse

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