TET-mediated active DNA demethylation: mechanism, function and beyond

Nature Reviews Genetics, Journal Year: 2017, Volume and Issue: 18(9), P. 517 - 534

Published: May 30, 2017

Language: Английский

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Reversing DNA Methylation: Mechanisms, Genomics, and Biological Functions

Cell, Journal Year: 2014, Volume and Issue: 156(1-2), P. 45 - 68

Published: Jan. 1, 2014

Language: Английский

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Role of TET enzymes in DNA methylation, development, and cancer

Genes & Development, Journal Year: 2016, Volume and Issue: 30(7), P. 733 - 750

Published: April 1, 2016

The pattern of DNA methylation at cytosine bases in the genome is tightly linked to gene expression, and abnormalities are often observed diseases. ten eleven translocation (TET) enzymes oxidize 5-methylcytosines (5mCs) promote locus-specific reversal methylation. TET genes, especially TET2 , frequently mutated various cancers, but how proteins contribute prevent onset maintenance these malignancies largely unknown. Here, we highlight recent advances understanding physiological function their role regulating transcription. In addition, discuss some key outstanding questions field.

Language: Английский

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Microbial genes, brain & behaviour - epigenetic regulation of the gut-brain axis

Genes Brain & Behavior, Journal Year: 2013, Volume and Issue: 13(1), P. 69 - 86

Published: Nov. 28, 2013

To date, there is rapidly increasing evidence for host-microbe interaction at virtually all levels of complexity, ranging from direct cell-to-cell communication to extensive systemic signalling, and involving various organs organ systems, including the central nervous system. As such, discovery that differential microbial composition associated with alterations in behaviour cognition has significantly contributed establishing microbiota-gut-brain axis as an extension well-accepted gut-brain concept. Many efforts have been focused on delineating a role this health disease, stress-related disorders such depression, anxiety irritable bowel syndrome neurodevelopmental autism. There also growing appreciation epigenetic mechanisms shaping brain behaviour. However, epigenetics informing interactions received little attention date. This despite fact are many plausible routes between host-microbiota dialogue. From new perspective we put forward novel, yet testable, hypotheses. Firstly, suggest gut-microbial products can affect chromatin plasticity within their host's turn leads changes neuronal transcription eventually alters host Secondly, argue microbiota important mediator gene-environment interactions. Finally, reason itself may be viewed entity. In conclusion, fields (neuro)epigenetics microbiology converging more interdisciplinary studies necessary unravel full range interaction.

Language: Английский

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Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders

Pharmacology & Therapeutics, Journal Year: 2014, Volume and Issue: 149, P. 150 - 190

Published: Dec. 27, 2014

Pathological fear and anxiety are highly debilitating and, despite considerable advances in psychotherapy pharmacotherapy they remain insufficiently treated many patients with PTSD, phobias, panic other disorders. Increasing preclinical clinical evidence indicates that pharmacological treatments including cognitive enhancers, when given as adjuncts to psychotherapeutic approaches [cognitive behavioral therapy extinction-based exposure therapy] enhance treatment efficacy, while using anxiolytics such benzodiazepines can undermine long-term success. The purpose of this review is outline the literature showing how interventions targeting neurotransmitter systems serotonin, dopamine, noradrenaline, histamine, glutamate, GABA, cannabinoids, neuropeptides (oxytocin, Y S, opioids) targets (neurotrophins BDNF FGF2, glucocorticoids, L-type-calcium channels, epigenetic modifications) well their downstream signaling pathways, augment extinction strengthen memory persistently models. Particularly promising discussed regard effects on specific aspects namely, acquisition, consolidation retrieval, protection from return (relapse) phenomena like spontaneous recovery, reinstatement renewal fear. We also highlight translational value preclinial research potential certain neurochemical with, for example d-cycloserine, yohimbine, cortisol, L-DOPA. current body reveals important new insights into neurobiology neurochemistry holds significant promise pharmacologically-augmented an improved approach treat trauma anxiety-related disorders a more efficient persistent way promoting enhanced symptom remission recovery.

Language: Английский

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What is memory? The present state of the engram

BMC Biology, Journal Year: 2016, Volume and Issue: 14(1)

Published: May 19, 2016

The mechanism of memory remains one the great unsolved problems biology. Grappling with question more than a hundred years ago, German zoologist Richard Semon formulated concept engram, lasting connections in brain that result from simultaneous “excitations”, whose precise physical nature and consequences were out reach biology his day. Neuroscientists now have knowledge tools to tackle this question, however, Forum brings together leading contemporary views on mechanisms what engram means today.

Language: Английский

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Is plasticity of synapses the mechanism of long-term memory storage?

npj Science of Learning, Journal Year: 2019, Volume and Issue: 4(1)

Published: July 2, 2019

Abstract It has been 70 years since Donald Hebb published his formalized theory of synaptic adaptation during learning. Hebb’s seminal work foreshadowed some the great neuroscientific discoveries following decades, including discovery long-term potentiation and other lasting forms plasticity, more recently residence memories in synaptically connected neuronal assemblies. Our understanding processes underlying learning memory dominated by view that synapses are principal site information storage brain. This received substantial support from research several model systems, with vast majority studies on topic corroborating a role for storage. Yet, despite neuroscience community’s best efforts, we still without conclusive proof reside at synapses. Furthermore, an increasing number non-synaptic mechanisms have emerged also capable acting as substrates. In this review, address key findings plasticity literature make these phenomena such attractive mechanisms. We then turn our attention to evidence questions reliance exclusively changes synapse attempt integrate opposing views.

Language: Английский

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The Emerging Field of Neuroepigenetics

Neuron, Journal Year: 2013, Volume and Issue: 80(3), P. 624 - 632

Published: Oct. 1, 2013

Language: Английский

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Whole-genome analysis of 5-hydroxymethylcytosine and 5-methylcytosine at base resolution in the human brain

Genome biology, Journal Year: 2014, Volume and Issue: 15(3)

Published: March 4, 2014

Abstract Background 5-methylcytosine (mC) can be oxidized by the tet methylcytosine dioxygenase (Tet) family of enzymes to 5-hydroxymethylcytosine (hmC), which is an intermediate mC demethylation and may also a stable epigenetic modification that influences chromatin structure. hmC particularly abundant in mammalian brains but its function currently unknown. A high-resolution hydroxymethylome map required fully understand human brain. Results We present genome-wide single-base resolution maps brain combined application Tet-assisted bisulfite sequencing sequencing. demonstrate hmCs increase markedly from fetal adult stage, brain, 13% all CpGs are highly hydroxymethylated with strong enrichment at genic regions distal regulatory elements. Notably, peaks identified 5′splicing sites exon-intron boundary, suggesting mechanistic link between splicing. report surprising transcription-correlated bias toward sense strand antisense gene bodies. Furthermore, negatively correlated H3K27me3-marked H3K9me3-marked repressive genomic regions, more enriched poised enhancers than active enhancers. Conclusions provide our data imply novel roles regulating splicing expression. Hydroxymethylation main status for large portion situated actively transcribed tuning these regions.

Language: Английский

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Mechanisms of cognitive dysfunction in CKD

Nature Reviews Nephrology, Journal Year: 2020, Volume and Issue: 16(8), P. 452 - 469

Published: March 31, 2020

Language: Английский

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