Ing1 functions in DNA demethylation by directing Gadd45a to H3K4me3

Schäfer, Andrea; Karaulanov, Emil; Stapf, Ulrike; Döderlein, Gabi; Niehrs, Christof

doi:10.1101/gad.186916.112

Cited by 53 publications

(43 citation statements)

References 75 publications

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“…GADD45 proteins participate in repair-based DNA demethylation by recruiting the base-excision or the nucleotide-excision repair machinery (BER and NER, respectively; Jung et al, 2007; Schäfer, 2013). Interestingly, it has been reported that Gadd45 gene expression can be induced by cellular stress (Hollander and Fornace, 2002), ultimately initiating GADD45-mediated DNA demethylation which, notably, seems to be restricted to single genes (Schmitz et al, 2009; Gavin et al, 2012; Schäfer et al, 2013), without affecting global DNA demethylation (Engel et al, 2009). …”

Section: Discussionmentioning

confidence: 99%

Oct4 Methylation-Mediated Silencing As an Epigenetic Barrier Preventing Müller Glia Dedifferentiation in a Murine Model of Retinal Injury

Reyes-Aguirre

Lamas

2016

Front. Neurosci.

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Müller glia (MG) is the most abundant glial type in the vertebrate retina. Among its many functions, it is capable of responding to injury by dedifferentiating, proliferating, and differentiating into every cell types lost to damage. This regenerative ability is notoriously absent in mammals. We have previously reported that cultured mammalian MG undergoes a partial dedifferentiation, but fails to fully acquire a progenitor phenotype and differentiate into neurons. This might be explained by a mnemonic mechanism comprised by epigenetic traits, such as DNA methylation. To achieve a better understanding of this epigenetic memory, we studied the expression of pluripotency-associated genes, such as Oct4, Nanog, and Lin28, which have been reported as necessary for regeneration in fish, at early times after NMDA-induced retinal injury in a mouse experimental model. We found that although Oct4 is expressed rapidly after damage (4 hpi), it is silenced at 24 hpi. This correlates with a significant decrease in the DNA methyltransferase Dnmt3b expression, which returns to basal levels at 24 hpi. By MS-PCR, we observed a decrease in Oct4 methylation levels at 4 and 12 hpi, before returning to a fully methylated state at 24 hpi. To demonstrate that these changes are restricted to MG, we separated these cells using a GLAST antibody coupled with magnetic beads. Finally, intravitreous administration of the DNA-methyltransferase inhibitor SGI-1027 induced Oct4 expression at 24 hpi in MG. Our results suggest that mammalian MG injury-induced dedifferentiation could be restricted by DNA methylation, which rapidly silences Oct4 expression, preventing multipotency acquisition.

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Section: Discussionmentioning

confidence: 99%

Oct4 Methylation-Mediated Silencing As an Epigenetic Barrier Preventing Müller Glia Dedifferentiation in a Murine Model of Retinal Injury

Reyes-Aguirre

Lamas

2016

Front. Neurosci.

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“…Gadd45a mediates nucleotide exchange DNA repair and thus demethylation (Barreto et al, 2007; Ma, Guo, Ming, & Song, 2009; Niehrs & Schafer, 2012). However, Gadd45a protein lacks a DNA binding domain and depends on tumor suppressor inhibitor of growth protein 1 (ING1) to recruit to promoters enriched with H3K4me3, which then triggers locus specific DNA demethylation (Schafer, Karaulanov, Stapf, Doderlein, & Niehrs, 2013). In short, epigenetic modifications include histone methylations, DNA methylation and demethylation, which coordinate to regulate lineage-specific gene expression.…”

Section: Epigenetic Regulation Of Adipose Developmentmentioning

confidence: 99%

Nutrigenomic regulation of adipose tissue development — role of retinoic acid: A review

et al. 2016

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To improve the efficiency of animal production, livestock have been extensively selected or managed to reduce fat accumulation and increase lean growth, which reduces intramuscular or marbling fat content. To enhance marbling, a better understanding of the mechanisms regulating adipogenesis is needed. Vitamin A has recently been shown to have a profound impact on all stages of adipogenesis. Retinoic acid, an active metabolite of vitamin A, activates both retinoic acid receptors (RAR) and retinoid X receptors (RXR), inducing epigenetic changes in key regulatory genes governing adipogenesis. Additionally, Vitamin D and folates interact with the retinoic acid receptors to regulate adipogenesis. In this review, we discuss nutritional regulation of adipogenesis, focusing on retinoic acid and its impact on epigenetic modifications of key adipogenic genes.

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“…ING1b is the most widely expressed isoform of ING1, while ING2a is the major isoform of ING2. Their tumor suppressor functions have been concerned with many biological processes including gene transcription, cell growth control, apoptosis, and cellular senescence [10,11]. Their role as tumor suppressors is supported by the fact that their expression is decreased or lost in many human tumors [12].…”

Section: Introductionmentioning

confidence: 99%

A novel crosstalk between the tumor suppressors ING1 and ING2 regulates androgen receptor signaling

et al. 2016

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Ing1 functions in DNA demethylation by directing Gadd45a to H3K4me3

Cited by 53 publications

References 75 publications

Oct4 Methylation-Mediated Silencing As an Epigenetic Barrier Preventing Müller Glia Dedifferentiation in a Murine Model of Retinal Injury

Oct4 Methylation-Mediated Silencing As an Epigenetic Barrier Preventing Müller Glia Dedifferentiation in a Murine Model of Retinal Injury

Nutrigenomic regulation of adipose tissue development — role of retinoic acid: A review

A novel crosstalk between the tumor suppressors ING1 and ING2 regulates androgen receptor signaling

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