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Repressed memories

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https://www.readbyqxmd.com/read/28430857/repurposed-drugs-targeting-eif2%C3%AE-p-mediated-translational-repression-prevent-neurodegeneration-in-mice
#1
Mark Halliday, Helois Radford, Karlijn A M Zents, Collin Molloy, Julie A Moreno, Nicholas C Verity, Ewan Smith, Catharine A Ortori, David A Barrett, Martin Bushell, Giovanna R Mallucci
Signalling through the PERK/eIF2α-P branch of the unfolded protein response plays a critical role in controlling protein synthesis rates in cells. This pathway is overactivated in brains of patients with Alzheimer's disease and related disorders and has recently emerged as a promising therapeutic target for these currently untreatable conditions. Thus, in mouse models of neurodegenerative disease, prolonged overactivation of PERK/eIF2α-P signalling causes sustained attenuation of protein synthesis, leading to memory impairment and neuronal loss...
April 19, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28428426/transgenerational-transmission-of-environmental-information-in-c-elegans
#2
Adam Klosin, Eduard Casas, Cristina Hidalgo-Carcedo, Tanya Vavouri, Ben Lehner
The environment experienced by an animal can sometimes influence gene expression for one or a few subsequent generations. Here, we report the observation that a temperature-induced change in expression from a Caenorhabditis elegans heterochromatic gene array can endure for at least 14 generations. Inheritance is primarily in cis with the locus, occurs through both oocytes and sperm, and is associated with altered trimethylation of histone H3 lysine 9 (H3K9me3) before the onset of zygotic transcription. Expression profiling reveals that temperature-induced expression from endogenous repressed repeats can also be inherited for multiple generations...
April 21, 2017: Science
https://www.readbyqxmd.com/read/28426734/study-of-deaths-by-suicide-of-homosexual-prisoners-in-nazi-sachsenhausen-concentration-camp
#3
Esther Cuerda-Galindo, Francisco López-Muñoz, Matthis Krischel, Astrid Ley
Living conditions in Nazi concentration camps were harsh and inhumane, leading many prisoners to commit suicide. Sachsenhausen (Oranienburg, Germany) was a concentration camp that operated from 1936 to 1945. More than 200,000 people were detained there under Nazi rule. This study analyzes deaths classified as suicides by inmates in this camp, classified as homosexuals, both according to the surviving Nazi files. This collective was especially repressed by the Nazi authorities. Data was collected from the archives of Sachsenhausen Memorial and the International Tracing Service in Bad Arolsen...
2017: PloS One
https://www.readbyqxmd.com/read/28410989/polycomb-repressive-complex-2-mediated-chromatin-repression-guides-effector-cd8-t-cell-terminal-differentiation-and-loss-of-multipotency
#4
Simon M Gray, Robert A Amezquita, Tianxia Guan, Steven H Kleinstein, Susan M Kaech
Understanding immunological memory formation depends on elucidating how multipotent memory precursor (MP) cells maintain developmental plasticity and longevity to provide long-term immunity while other effector cells develop into terminally differentiated effector (TE) cells with limited survival. Profiling active (H3K27ac) and repressed (H3K27me3) chromatin in naive, MP, and TE CD8(+) T cells during viral infection revealed increased H3K27me3 deposition at numerous pro-memory and pro-survival genes in TE relative to MP cells, indicative of fate restriction, but permissive chromatin at both pro-memory and pro-effector genes in MP cells, indicative of multipotency...
April 18, 2017: Immunity
https://www.readbyqxmd.com/read/28366226/selective-deletion-of-apolipoprotein-e-in-astrocytes-ameliorates-the-spatial-learning-and-memory-deficits-in-alzheimer-s-disease-app-ps1-mice-by-inhibiting-tgf-%C3%AE-smad2-stat3-signaling
#5
Jin-Yu Zheng, Jian Sun, Chun-Mei Ji, Lin Shen, Zhong-Jun Chen, Peng Xie, Yuan-Zhao Sun, Ru-Tong Yu
Astrocytes and apolipoprotein E (apoE) play critical roles in cognitive function, not only under physiological conditions but also in some pathological situations, particularly in the pathological progression of Alzheimer's disease (AD). The regulatory mechanisms underlying the effect of apoE, derived from astrocytes, on cognitive deficits during AD pathology development are unclear. In this study, we generated amyloid precursor protein/apoE knockout (APP/apoE(KO)) and APP/glial fibrillary acidic protein (GFAP)-apoE(KO) mice (the AD mice model used in this study was based on the APP-familial Alzheimer disease overexpression) to investigate the role of apoE, derived from astrocytes, in AD pathology and cognitive function...
March 11, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28346453/activity-induced-histone-modifications-govern-neurexin-1-mrna-splicing-and-memory-preservation
#6
Xinlu Ding, Sanxiong Liu, Miaomiao Tian, Wenhao Zhang, Tao Zhu, Dongdong Li, Jiawei Wu, HaiTeng Deng, Yichang Jia, Wei Xie, Hong Xie, Ji-Song Guan
Epigenetic mechanisms regulate the formation, consolidation and reconsolidation of memories. However, the signaling path from neuronal activation to epigenetic modifications within the memory-related brain circuit remains unknown. We report that learning induces long-lasting histone modifications in hippocampal memory-activated neurons to regulate memory stability. Neuronal activity triggers a late-onset shift in Nrxn1 splice isoform choice at splicing site 4 by accumulating a repressive histone marker, H3K9me3, to modulate the splicing process...
March 27, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28346433/a-cytosolic-ezh1-isoform-modulates-a-prc2-ezh1-epigenetic-adaptive-response-in-postmitotic-cells
#7
Beatrice Bodega, Federica Marasca, Valeria Ranzani, Alessandro Cherubini, Francesco Della Valle, Maria Victoria Neguembor, Michel Wassef, Alessio Zippo, Chiara Lanzuolo, Massimiliano Pagani, Valerio Orlando
The evolution of chromatin-based epigenetic cell memory may be driven not only by the necessity for cells to stably maintain transcription programs, but also by the need to recognize signals and allow plastic responses to environmental stimuli. The mechanistic role of the epigenome in adult postmitotic tissues, however, remains largely unknown. In vertebrates, two variants of the Polycomb repressive complex (PRC2-Ezh2 and PRC2-Ezh1) control gene silencing via methylation of histone H3 on Lys27 (H3K27me). Here we describe a reversible mechanism that involves a novel isoform of Ezh1 (Ezh1β)...
March 27, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28342717/slow-chromatin-dynamics-allow-polycomb-target-genes-to-filter-fluctuations-in-transcription-factor-activity
#8
Scott Berry, Caroline Dean, Martin Howard
Genes targeted by Polycomb repressive complex 2 (PRC2) are regulated in cis by chromatin modifications and also in trans by diffusible regulators such as transcription factors. Here, we introduce a mathematical model in which transcription directly antagonizes Polycomb silencing, thereby linking these cis- and trans-regulatory inputs to gene expression. The model is parameterized by recent experimental data showing that PRC2-mediated repressive chromatin modifications accumulate extremely slowly. The model generates self-perpetuating, bistable active and repressed chromatin states that persist through DNA replication, thereby ensuring high-fidelity transmission of the current chromatin state...
March 21, 2017: Cell Systems
https://www.readbyqxmd.com/read/28304152/reprogramming-of-histone-methylation-controls-the-differentiation-of-monocytes-into-macrophages
#9
Qi-Fan Zheng, Hui-Min Wang, Zhan-Feng Wang, Jin-Yang Liu, Qi Zhang, Li Zhang, Yuan-Hua Lu, Han You, Guang-Hui Jin
Subset heterogeneity of the mononuclear phagocyte system (MPS) is controlled by defined transcriptional networks and programs; however, the dynamic establishment of programs that control broad, orchestrated expression of transcription factors (TFs) during the progression of monocyte-into-phagocyte (MP) differentiation remains largely unexplored. By using chromatin immunoprecipitation assays, we show the extensive trimethylation of histone H3 lysine 4 (H3K4me3) as well as histone H3 lysine 27 (H3K27me3) occupancy with broad footprints at the promoters of MP differentiation-related TFs, such as HOXA and FOXO genes, KLF4, IRF8 and others...
March 17, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28302795/causal-role-for-inheritance-of-h3k27me3-in-maintaining-the-off-state-of-a-drosophila-hox-gene
#10
Rory T Coleman, Gary Struhl
Many eukaryotic cells can respond to transient environmental or developmental stimuli with heritable changes in gene expression that are associated with nucleosome modifications. However, it remains uncertain whether modified nucleosomes play a causal role in transmitting such epigenetic memories, as opposed to controlling or merely reflecting transcriptional states inherited by other means. Here, we provide in vivo evidence that H3K27 trimethylated nucleosomes, once established at a repressed Drosophila HOX gene, remain heritably associated with that gene and can carry the memory of the silenced state through multiple rounds of replication, even when the capacity to copy the H3K27me3 mark to newly incorporated nucleosomes is diminished or abolished...
April 7, 2017: Science
https://www.readbyqxmd.com/read/28302792/propagation-of-polycomb-repressed-chromatin-requires-sequence-specific-recruitment-to-dna
#11
Friederike Laprell, Katja Finkl, Jürg Müller
Epigenetic inheritance models posit that during Polycomb repression, Polycomb repressive complex 2 (PRC2) propagates histone H3 lysine 27 trimethylation (H3K27me3) independently of DNA sequence. We show that insertion of Polycomb response element (PRE) DNA into the Drosophila genome creates extended domains of H3K27me3-modified nucleosomes in the flanking chromatin and causes repression of a linked reporter gene. After excision of PRE DNA, H3K27me3 nucleosomes become diluted with each round of DNA replication, and reporter gene repression is lost...
April 7, 2017: Science
https://www.readbyqxmd.com/read/28279665/multiple-sevoflurane-anesthesia-in-pregnant-mice-inhibits-neurogenesis-of-fetal-hippocampus-via-repressing-transcription-factor-pax6
#12
Fang Fang, Ruixue Song, Xiaomin Ling, Mengyuan Peng, Zhanggang Xue, Jing Cang
Sevoflurane is widely used in non-obstetric surgeries of pregnant women, but its influences on fetal brain are still not fully known. We set out to assess the effects of multiple maternal sevoflurane exposure on neurogenesis and cognitive dysfunction in fetus and offspring. Pregnant mice (gestational day 15.5) and cultured mouse neural stem cells (NSCs) received daily sevoflurane exposure (2.5%×2h and 4.1%×2h respectively) for three consecutive days. Cognitive function of the offspring was determined with the Morris water maze...
April 15, 2017: Life Sciences
https://www.readbyqxmd.com/read/28246360/multiple-histone-lysine-methyltransferases-are-required-for-the-establishment-and-maintenance-of-hiv-1-latency
#13
Kien Nguyen, Biswajit Das, Curtis Dobrowolski, Jonathan Karn
We showed previously that the histone lysine methyltransferase (HKMT) H3K27me3 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and is required for the maintenance of HIV-1 latency in Jurkat T cells. Here we show, by using chromatin immunoprecipitation experiments, that both PRC2 and euchromatic histone-lysine N-methyltransferase 2 (EHMT2), the G9a H3K9me2-3 methyltransferase, are highly enriched at the proviral 5' long terminal repeat (LTR) and rapidly displaced upon proviral reactivation...
February 28, 2017: MBio
https://www.readbyqxmd.com/read/28219680/the-regulation-of-transcriptional-repression-in-hypoxia
#14
Miguel A S Cavadas, Alex Cheong, Cormac T Taylor
A sufficient supply molecular oxygen is essential for the maintenance of physiologic metabolism and bioenergetic homeostasis for most metazoans. For this reason, mechanisms have evolved for eukaryotic cells to adapt to conditions where oxygen demand exceeds supply (hypoxia). These mechanisms rely on the modification of pre-existing proteins, translational arrest and transcriptional changes. The hypoxia inducible factor (HIF; a master regulator of gene induction in response to hypoxia) is responsible for the majority of induced gene expression in hypoxia...
February 20, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28208656/primetime-for-learning-genes
#15
REVIEW
Joyce Keifer
Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells...
February 11, 2017: Genes
https://www.readbyqxmd.com/read/28027601/hysteresis-in-myo-inositol-utilization-by-salmonella-typhimurium
#16
Jessica Hellinckx, Thilo M Fuchs
Growth of Salmonella enterica serovar Typhimurium strain 14028 with myo-inositol (MI) as the sole carbon and energy source is characterized by a bistable phenotype that manifests in a growth phenotype with an extraordinarily long and length-variable lag phase. However, in the presence of hydrogen carbonate, in the absence of IolR that represses the MI degradation pathway, or if cells are already adapted to minimal medium (MM) with MI, the lag phase is drastically shortened, and the bistable phenotype is abolished...
April 2017: MicrobiologyOpen
https://www.readbyqxmd.com/read/28018990/the-tcf1-bcl6-axis-counteracts-type-i-interferon-to-repress-exhaustion-and-maintain-t-cell-stemness
#17
Tuoqi Wu, Yun Ji, E Ashley Moseman, Haifeng C Xu, Monica Manglani, Martha Kirby, Stacie M Anderson, Robin Handon, Elizabeth Kenyon, Abdel Elkahloun, Weiwei Wu, Philipp A Lang, Luca Gattinoni, Dorian B McGavern, Pamela L Schwartzberg
During chronic viral infections and in cancer, T cells become dysfunctional, a state known as T cell exhaustion. Although it is well recognized that memory CD8 T cells account for the persistence of CD8 T cell immunity after acute infection, how exhausted T cells persist remains less clear. Using chronic infection with lymphocytic choriomeningitis virus clone 13 and tumor samples, we demonstrate that CD8 T cells differentiate into a less exhausted TCF1(high) and a more exhausted TCF1(low) population. Virus-specific TCF1(high) CD8 T cells, which resemble T follicular helper (TFH) cells, persist and recall better than do TCF1(low) cells and act as progenitor cells to replenish TCF1(low) cells...
December 23, 2016: Science Immunology
https://www.readbyqxmd.com/read/28011866/the-aryl-hydrocarbon-receptor-controls-cell-fate-decisions-in-b-cells
#18
Bharat Vaidyanathan, Ashutosh Chaudhry, William T Yewdell, Davide Angeletti, Wei-Feng Yen, Adam K Wheatley, Christopher A Bradfield, Adrian B McDermott, Jonathan W Yewdell, Alexander Y Rudensky, Jayanta Chaudhuri
Generation of cellular heterogeneity is an essential feature of the adaptive immune system. This is best exemplified during humoral immune response when an expanding B cell clone assumes multiple cell fates, including class-switched B cells, antibody-secreting plasma cells, and memory B cells. Although each cell type is essential for immunity, their generation must be exquisitely controlled because a class-switched B cell cannot revert back to the parent isotype, and a terminally differentiated plasma cell cannot contribute to the memory pool...
January 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27992519/site-dependent-differences-in-dna-methylation-and-their-impact-on-plant-establishment-and-phosphorus-nutrition-in-populus-trichocarpa
#19
Brigitte Schönberger, Xiaochao Chen, Svenja Mager, Uwe Ludewig
The propagation via clonal stem cuttings is a frequent practice in tree plantations. Despite their clonal origin, the trees establish differently according to weather, temperature and nutrient availability, as well as the presence of various stresses. Here, clonal Populus trichocarpa (cv. Muhle Larson) cuttings from different sites were transferred into a common, fully nutrient supplied environment. Despite identical underlying genetics, stem cuttings derived from sites with lower phosphorus availability established worse, independent of phosphorus (P) level after transplantation...
2016: PloS One
https://www.readbyqxmd.com/read/27984208/oral-administration-of-grape-seed-polyphenol-extract-restores-memory-deficits-in-chronic-cerebral-hypoperfusion-rats
#20
Chen Chen, Yake Zheng, Tianwen Wu, Chuanjie Wu, Xuan Cheng
Chronic cerebral hypoperfusion (CCH) has been recognized as an important cause of both vascular dementia and Alzheimer's disease (AD), the two most prominent neurodegenerative diseases causing memory impairment in the elderly. However, an effective therapy for CCH-induced memory impairment has not yet been established. Grape seed polyphenol extract (GSPE) has powerful antioxidant properties and protects neurons and glia during ischemic injury, but its potential use in the prevention of CCH-induced memory impairment has not yet been investigated...
April 2017: Behavioural Pharmacology
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