SIRT1-mediated deacetylation of MeCP2 contributes to BDNF expression

Zocchi, Loredana; Sassone–Corsi, Paolo

doi:10.4161/epi.20733

Cited by 111 publications

(104 citation statements)

References 32 publications

(47 reference statements)

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“…SIRT1 has also been demonstrated to deacetylate methyl-CpG-binding protein 2 (MeCP2). Deacetylated MeCP2 is released from methylated CpG sites within the brain-derived neurotrophic factor promoter, thus leading to increased expression of brainderived neurotrophic factor, a known neuroprotective protein [46]. SIRT1 may also regulate a neuroprotective phenotype through the deacetylation and thus activation or inhibition of transcription factors, transcriptional co-activators, and nuclear receptors [37].…”

Section: Acetylationmentioning

confidence: 99%

Ischemic Preconditioning Alters the Epigenetic Profile of the Brain from Ischemic Intolerance to Ischemic Tolerance

et al. 2013

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Ischemic preconditioning is an innate neuroprotective mechanism in which a sub-injurious ischemic exposure increases the brain's ability to withstand a subsequent, normally injurious ischemic insult. Part of ischemic preconditioning neuroprotection stems from an epigenetic reprogramming of the brain to a phenotype of ischemic tolerance, which results in a gene expression profile different from that observed in the non-injured and ischemia-injured brains. Such neuroprotective reprograming, activated by ischemic preconditioning, requires specific changes in DNA accessibility coordinated with activation of transcriptional activator and repressor proteins, which allows for expression of specific neuroprotective proteins despite a general repression of gene expression. In this review we examine the effects of injurious ischemia and ischemic preconditioning on the regulation of DNA methylation, histone post-translational modifications, and non-coding RNA expression. There is increasing interest in the role of epigenetics in disease pathobiology, and whether and how pharmacological manipulation of epigenetic processes may allow for ischemic neuroprotection. Therefore, a better understanding of the epigenomic determinants underlying the modulation of gene expression that lead to ischemic tolerance or cell death offers the promise of novel neuroprotective therapies that target global reprograming of genomic activity versus individual cellular signaling pathways.

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Section: Acetylationmentioning

confidence: 99%

Ischemic Preconditioning Alters the Epigenetic Profile of the Brain from Ischemic Intolerance to Ischemic Tolerance

et al. 2013

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“…This suggested a potential mechanism (regulation of gene expression by neuronal activity) by which MeCP2 mutation could lead to the developmental abnormalities observed in neurons [117,118]. Recently, it was shown that MeCP2 is acetylated by p300 and that SIRT1 mediates its deacetylation [119]. This suggests a functional interplay between 2 critical epigenetic regulators, MeCP2 and SIRT1, modulating MeCP2 binding to the BDNF promoter in specific brain regions.…”

Section: Mecp2 Duplication Syndromementioning

confidence: 99%

Epigenetics, Autism Spectrum, and Neurodevelopmental Disorders

2013

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Epigenetic marks are modifications of DNA and histones. They are considered to be permanent within a single cell during development, and are heritable across cell division. Programming of neurons through epigenetic mechanisms is believed to be critical in neural development. Disruption or alteration in this process causes an array of neurodevelopmental disorders, including autism spectrum disorders (ASDs). Recent studies have provided evidence for an altered epigenetic landscape in ASDs and demonstrated the central role of epigenetic mechanisms in their pathogenesis. Many of the genes linked to the ASDs encode proteins that are involved in transcriptional regulation and chromatin remodeling. In this review we highlight selected neurodevelopmental disorders in which epigenetic dysregulation plays an important role. These include Rett syndrome, fragile X syndrome, Prader-Willi syndrome, Angelman syndrome, and Kabuki syndrome. For each of these disorders, we discuss how advances in our understanding of epigenetic mechanisms may lead to novel therapeutic approaches.

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“…It would be intriguing to investigate such mechanisms directly after nerve injury where calcium-dependent depolarization occurs. Promoter binding of MECP2 to the Bdnf promoter can also be regulated by acetylation and deacetylation via the histone modifying enzymes EP300 and SIRT1, respectively [75], or by phosphorylation [76]. Surprisingly, binding of MECP2 was also reported earlier to repress Bdnf expression, depending on the specific promoter region likely regulating the expression of selected BDNF isoforms [77,78].…”

Section: Dna Methylation In Neuronal Plasticity and Axonal Injurymentioning

confidence: 99%

Epigenetic Regulation of Axon Outgrowth and Regeneration in CNS Injury: The First Steps Forward

2013

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Inadequate axonal sprouting and lack of regeneration limit functional recovery following neurologic injury, such as stroke, brain, and traumatic spinal cord injury. Recently, the enhancement of the neuronal regenerative program has led to promising improvements in axonal sprouting and regeneration in animal models of axonal injury. However, precise knowledge of the essential molecular determinants of this regenerative program remains elusive, thus limiting the choice of fully effective therapeutic strategies. Given that molecular regulation of axonal outgrowth and regeneration requires carefully orchestrated waves of gene expression, both temporally and spatially, epigenetic changes may be an ideal regulatory mechanism to address this unique need. While recent evidence suggests that epigenetic modifications could contribute to the regulation of axonal outgrowth and regeneration following axonal injury in models of stroke, and spinal cord and optic nerve injury, a number of unanswered questions remain. Such questions require systematic investigation of the epigenetic landscape between regenerative and non-regenerative conditions for the potential translation of this knowledge into regenerative strategies in human spinal and brain injury, as well as stroke.

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SIRT1-mediated deacetylation of MeCP2 contributes to BDNF expression

Cited by 111 publications

References 32 publications

Ischemic Preconditioning Alters the Epigenetic Profile of the Brain from Ischemic Intolerance to Ischemic Tolerance

Ischemic Preconditioning Alters the Epigenetic Profile of the Brain from Ischemic Intolerance to Ischemic Tolerance

Epigenetics, Autism Spectrum, and Neurodevelopmental Disorders

Epigenetic Regulation of Axon Outgrowth and Regeneration in CNS Injury: The First Steps Forward

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