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| Open AccessA comprehensive map coupling histone modifications with gene regulation in adult dopaminergic and serotonergic neurons
The limited size of some neuronal types and their entangled environment renders it difficult to study their transcription regulation. Here the authors present a comparative analysis of histone modifications and transcription in dopaminergic and serotonergic neurons and embryonic neural progenitors.
- Erik Södersten
- , Konstantinos Toskas
- & Johan Holmberg
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Article
| Open AccessEpigenetic modulation of inflammation and synaptic plasticity promotes resilience against stress in mice
Polyphenols have partial antidepressant effect without known mechanism. Here, the authors identify two phytochemicals from bioactive dietary polyphenols, show their antidepressant effect in a rodent model of depression, and that this effect is mediated by epigenetic and anti-inflammatory mechanisms.
- Jun Wang
- , Georgia E. Hodes
- & Giulio M. Pasinetti
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| Open AccessEnvironmental enrichment increases transcriptional and epigenetic differentiation between mouse dorsal and ventral dentate gyrus
Environmental enrichment has functional and molecular effects on mammalian hippocampus. Here, Zhang and colleagues show that environmental enrichment of mice is correlated with dorsal-ventral asymmetry in transcription and DNA methylation of the dentate gyrus.
- Tie-Yuan Zhang
- , Christopher L. Keown
- & Michael J. Meaney
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| Open AccessTrithorax dependent changes in chromatin landscape at enhancer and promoter regions drive female puberty
Before the onset of puberty, Polycomb proteins repress the expression of Kiss1 in KNDy neurons of the arcuate nucleus. Here, by CRISPR-Cas9-directed epigenome editing and RNAi, the authors show that coordinated action of Mll proteins at the Kiss1 promoter and enhancer is required for correct timing of puberty.
- Carlos A. Toro
- , Hollis Wright
- & Alejandro Lomniczi
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Article
| Open AccessChemogenomic analysis reveals key role for lysine acetylation in regulating Arc stability
The activity-regulated cytoskeleton-associated protein (Arc) has been implicated in synaptic plasticity and memory consolidation. Here the authors show that Arc acetylation regulates its stability and identify small molecules that modulate Arc expression.
- Jasmin Lalonde
- , Surya A. Reis
- & Stephen J. Haggarty
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| Open AccessGenome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus
Most SNPs are located in non-coding genomic regions and their function remains elusive. Here, the authors perform a genome-wide scan of expression and DNA methylation quantitative trait loci in human hippocampal tissue to provide a resource for the functional interpretation of SNPs in brain disorders.
- Herbert Schulz
- , Ann-Kathrin Ruppert
- & Sven Cichon
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Article
| Open AccessLSD1 protects against hippocampal and cortical neurodegeneration
“LSD1 is a histone demethylase that plays many roles during development. Here, the authors provide evidence that loss of LSD1 in adult mice leads to paralysis and neurodegeneration in the hippocampus and cortex and suggest a potential link between LSD1 and human neurodegenerative disease.
- Michael A. Christopher
- , Dexter A. Myrick
- & David J. Katz
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| Open AccessCDYL suppresses epileptogenesis in mice through repression of axonal Nav1.6 sodium channel expression
Alterations in intrinsic plasticity are important in epilepsy. Here the authors show that the epigenetic factor CDYL regulates the gene expression of the voltage gated sodium channel, Nav1.6, which contributes to seizures in a rat model of epilepsy.
- Yongqing Liu
- , Shirong Lai
- & Zhuo Huang
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Article
| Open AccessMir-132/212 is required for maturation of binocular matching of orientation preference and depth perception
miR-132/212 has been implicated in ocular dominance plasticity during the critical period. Here the authors show that miR-132/212 regulates the expression of genes involved in visual cortex maturation, and that mice lack miR-132/212 show deficits in binocular matching of orientation preferences, which leads to impaired depth perception.
- Raffaele Mazziotti
- , Laura Baroncelli
- & Tommaso Pizzorusso
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| Open AccessA peripheral epigenetic signature of immune system genes is linked to neocortical thickness and memory
Cortical thickness has high heritability estimates and is known to be influenced by genetic factors. Here, Freytag and colleagues show that DNA methylation patterns of peripheral blood monocytes are also correlated with cortical thickness and memory performance in human.
- Virginie Freytag
- , Tania Carrillo-Roa
- & Andreas Papassotiropoulos
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| Open AccessDelaying histone deacetylase response to injury accelerates conversion into repair Schwann cells and nerve regeneration
Brüggeret al. identify part of the molecular machinery that controls Schwann cell development after peripheral nerve injury. Inhibiting HDAC1/2 early after injury enhances nerve regeneration and promotes functional recovery.
- Valérie Brügger
- , Mert Duman
- & Claire Jacob
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Article
| Open AccessShifting transcriptional machinery is required for long-term memory maintenance and modification in Drosophila mushroom bodies
Transcriptional regulation is necessary for maintaining long-term memories (LTM) but the mechanistic details are not completely defined. Here the authors identify transcriptional machinery and histone modifiers required for LTM maintenance inDrosophilaand show that transcriptional regulation for LTM maintenance is distinct from that for LTM formation.
- Yukinori Hirano
- , Kunio Ihara
- & Minoru Saitoe
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Article
| Open AccessLongitudinal assessment of neuronal 3D genomes in mouse prefrontal cortex
Chromosome conformation is a dynamic process, especially in brain. Here, Mitchell and colleagues devise a method they call NeuroDam that can prospectively tag chromosome conformation in the mouse brain in vivo, and longitudinally assess long range chromosome looping weeks and months later.
- Amanda C. Mitchell
- , Behnam Javidfar
- & Schahram Akbarian
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| Open AccessThe microRNA cluster miR-183/96/182 contributes to long-term memory in a protein phosphatase 1-dependent manner
Protein phosphatase1 (PP1), a signalling and transcriptional regulator, and epigenetic modulator is known to be a memory suppressor. Here the authors show that memory control by PP1 involves the microRNA cluster miR-183/96/182, and that this cluster is selectively regulated during memory formation in mice.
- Bisrat T. Woldemichael
- , Ali Jawaid
- & Isabelle M. Mansuy
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| Open AccessBehavioural traits propagate across generations via segregated iterative-somatic and gametic epigenetic mechanisms
Physiological effects of psychological stress and infection in mothers can increase the incidence of anxiety and psychiatric diseases in offsprings and in subsequent generation. Here, Miklos Toth and colleagues show that intergenerational inheritance of neurological traits is propagated across multiple generations independently by parallel non-genetic mechanisms involving independent segregation of epigenetic specific loci.
- Emma Mitchell
- , Shifra L. Klein
- & Miklos Toth
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| Open AccessGenetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum
This genome-wide association study identifies five significant SNPs in two loci which are associated with the epigenetic age of post-mortem cerebellar tissue according to a DNA methylation based biomarker of human aging.
- Ake T. Lu
- , Eilis Hannon
- & Steve Horvath
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Article
| Open AccessEvolutionary signals of selection on cognition from the great tit genome and methylome
The great tit (Parus major) is known for its complex social-cognitive behaviour. Here, the authors sequence genomes of the great tit and show genes related to learning and cognition in regions under positive selection, as well as neuronal non-CpG methylation patterns similar to those observed in mammals.
- Veronika N. Laine
- , Toni I. Gossmann
- & Martien A. M. Groenen
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Article
| Open AccessLSD1 co-repressor Rcor2 orchestrates neurogenesis in the developing mouse brain
Epigenetic regulation plays a key role in cortical development. Here the authors show that Rcor2, a co-repressor of the histone demethylase LSD1/KDM1A complex, regulates neural progenitor cell proliferation and cortical neurogenesis by repressing sonic hedgehog signaling.
- Yixuan Wang
- , Qian Wu
- & Xiaoqun Wang
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Article
| Open AccessNeuronal development is promoted by weakened intrinsic antioxidant defences due to epigenetic repression of Nrf2
Neurons in the brain are more susceptible to oxidative stress than astroglial cells but the molecular basis and biological reasons for this are poorly understood. Here the authors show that developing cortical neurons have reduced levels of the antioxidant transcription factor Nrf2 due to epigenetic silencing and that this is necessary for proper neuronal development.
- Karen F.S. Bell
- , Bashayer Al-Mubarak
- & Giles E. Hardingham
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Early life stress in fathers improves behavioural flexibility in their offspring
Traumatic events in one generation can affect the behaviour of their offspring. Here the authors subject male mouse pups to traumatic stress and find that their offspring display improved goal-directed behaviours associated with epigenetic changes of the mineralocorticoid receptor gene.
- Katharina Gapp
- , Saray Soldado-Magraner
- & Isabelle M. Mansuy
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Loss of neuronal 3D chromatin organization causes transcriptional and behavioural deficits related to serotonergic dysfunction
It is becoming increasingly clear that the three-dimensional organization of chromatin within the nucleus plays a role in regulating gene expression. Here, Ito et al.demonstrate that the disruption of chromocenter clustering in mature neuronal cells results in specific transcriptional and behavioural defects in mice.
- Satomi Ito
- , Adriana Magalska
- & Angel Barco