Inhibition of Histone Methyltransferases SUV39H1 and G9a Leads to Neuroprotection in an <i>in vitro</i> Model of Cerebral Ischemia

Schweizer, Sophie; Harms, Christoph; Lerch, Heike; Karlow, Jennifer A.; Hecht, Jochen; Yildirim, Ferah; Meisel, Andreas; Märschenz, Stefanie

doi:10.1038/jcbfm.2015.99

Cited by 40 publications

(26 citation statements)

References 41 publications

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“…It remains ambiguous whether the effects of chaetocin are entirely mediated through SUV39H and the specificity of chaetocin has been called into question20. Similar to our study, Schweizer et al 21. have reported that chaetocin administration is associated with neuroprotection in an in vitro model of cerebral ischaemia.…”

Section: Discussionsupporting

confidence: 70%

The histone H3K9 methyltransferase SUV39H links SIRT1 repression to myocardial infarction

et al. 2017

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Myocardial infarction (MI) dampens heart function and poses a great health risk. The class III deacetylase sirtuin 1 (SIRT1) is known to confer cardioprotection. SIRT1 expression is downregulated in the heart by a number of stress stimuli that collectively drive the pathogenesis of MI, although the underlying mechanism remains largely obscure. Here we show that in primary rat neonatal ventricular myocytes (NRVMs), ischaemic or oxidative stress leads to a rapid upregulation of SUV39H, the mammalian histone H3K9 methyltransferase, paralleling SIRT1 downregulation. Compared to wild-type littermates, SUV39H knockout mice are protected from MI. Likewise, suppression of SUV39H activity with chaetocin attenuates cardiac injury following MI. Mechanistically, SUV39H cooperates with heterochromatin protein 1 gamma (HP1γ) to catalyse H3K9 trimethylation on the SIRT1 promoter and represses SIRT1 transcription. SUV39H augments intracellular ROS levels in a SIRT1-dependent manner. Our data identify a previously unrecognized role for SUV39H linking SIRT1 trans-repression to myocardial infarction.

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Section: Discussionsupporting

confidence: 70%

The histone H3K9 methyltransferase SUV39H links SIRT1 repression to myocardial infarction

et al. 2017

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“…Its role is complex and may differentially affect gene expression, depending on temporal and spatial changes on the tissue level. Studies of animal and in vitro models of stroke demonstrated that histone methylation is affecting stroke severity during aging [ 55 ] and neuronal resistance in a model of hypoxic metabolic stress [ 56 ]. Besides that, studies implicated the connection of histone methylation with proinflammatory cytokines [ 57 ].…”

Section: Epigenetic Regulation Of Immune Response In Strokementioning

confidence: 99%

Genetic Aspects of Inflammation and Immune Response in Stroke

Nikolić

Janković

Petrović³

et al. 2020

IJMS

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Genetic determinants play important role in the complex processes of inflammation and immune response in stroke and could be studied in different ways. Inflammation and immunomodulation are associated with repair processes in ischemic stroke, and together with the concept of preconditioning are promising modes of stroke treatment. One of the important aspects to be considered in the recovery of patients after the stroke is a genetic predisposition, which has been studied extensively. Polymorphisms in a number of candidate genes, such as IL-6, BDNF, COX2, CYPC19, and GPIIIa could be associated with stroke outcome and recovery. Recent GWAS studies pointed to the variant in genesPATJ and LOC as new genetic markers of long term outcome. Epigenetic regulation of immune response in stroke is also important, with mechanisms of histone modifications, DNA methylation, and activity of non-coding RNAs. These complex processes are changing from acute phase over the repair to establishing homeostasis or to provoke exaggerated reaction and death. Pharmacogenetics and pharmacogenomics of stroke cures might also be evaluated in the context of immuno-inflammation and brain plasticity. Potential novel genetic treatment modalities are challenged but still in the early phase of the investigation.

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“…Aberrant regulation of those MAPKs is also related to numerous pathological conditions, as well as cancer.Recent studies have shown that arginine and lysine methylation also regulate the activities of MAPKs [73]- [75] . In invitro study of rat model, effects of inhibition of the repressing H3K9 histone methyltransferases SUV39H1 and G9a (responsible for H3K9 methylation) on neuronal survival and shelter in O 2 glucose deprivation atmosphere (OGD), BDNF gene expression was upregulated around promoter I, II and III selected in cerebral ishchemia [76] . Hypoxic environment in cancer cells are related with the initiation of methyl transferase G9a activity inhibiting demethylation.…”

Section: Histone Methylationmentioning

confidence: 99%

Histone Lysine Methylation: A Potential New Treatment Target with Respect to BDNF Gene in Type 2 Diabetic Retinopathy

Priyam¹

2019

IJRASET

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Type 2 diabetic retinopathy (T2DR) is a highly developed manifestation of diabetic retinopathy along with a prominent cause of sightlessness on a global scale. Brain-derived neurotrophic factor (BDNF), which is an associate of neurotrophin family of proteins and enciphered by the BDNF gene is very effectual in shielding retinas from abnormally high blood sugar associated with diabetes in-vitro. Till date, very less number of facts with respect to epigenetic modification is known in T2DR and future aspect associated with epigenetic studies can be explored in this slow progressing disease. Epigenetics have now turned out to be a crucial field of study in bioscience experimentation which regulates gene expression and change their function without any alteration in the DNA sequence in diabetic environment. Histone lysine methylatio take part in alteration of chromatin structure and regulation of gene expression. After going through the available literature, it can be hypothesized that by regulating H3K9 methylation which is a repressive mark, expression level of BDNF can be regulated which in turn can normalize the BDNF-TrkB signaling pathway and may protect apoptosis of human retinal cells in T2DR promoting their survival. mechanizable approach into histone modification may provide the mode for therapeutic function of drugs in T2DR. The present review is focused on histone methylation (H3K9) with respect to BDNF gene expression related to pathogenesis in T2DR and might be helpful for therapeutic purpose.

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Inhibition of Histone Methyltransferases SUV39H1 and G9a Leads to Neuroprotection in an in vitro Model of Cerebral Ischemia

Cited by 40 publications

References 41 publications

The histone H3K9 methyltransferase SUV39H links SIRT1 repression to myocardial infarction

The histone H3K9 methyltransferase SUV39H links SIRT1 repression to myocardial infarction

Genetic Aspects of Inflammation and Immune Response in Stroke

Histone Lysine Methylation: A Potential New Treatment Target with Respect to BDNF Gene in Type 2 Diabetic Retinopathy

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