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Chromatin memory

Timothy J Jarome, Rishi K Devulapalli
Cellular models of memory formation have focused on the need for protein synthesis. Recently, evidence has emerged that protein degradation mediated by the ubiquitin-proteasome system (UPS) is also important for this process. This has led to revised cellular models of memory formation that focus on a balance between protein degradation and synthesis. However, protein degradation is only one function of the UPS. Studies using single-celled organisms have shown that non-proteolytic ubiquitin-proteasome signaling is involved in histone modifications and DNA methylation, suggesting that ubiquitin and the proteasome can regulate chromatin remodeling independent of protein degradation...
March 1, 2018: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
Federica Marasca, Beatrice Bodega, Valerio Orlando
Cells and tissues are continuously exposed to a changing microenvironment, hence the necessity of a flexible modulation of gene expression that in complex organism have been achieved through specialized chromatin mechanisms. Chromatin-based cell memory enables cells to maintain their identity by fixing lineage specific transcriptional programs, ensuring their faithful transmission through cell division; in particular PcG-based memory system evolved to maintain the silenced state of developmental and cell cycle genes...
March 9, 2018: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
Jacqueline M Roberts, Monica L Vetter
The use of retinal organoids requires efficient differentiation from induced pluripotent stem cells (iPSCs). In this issue of Cell Reports, Wang et al. (2018) examine how the chromatin landscape after iPSC programming predicts their ability to differentiate into retinal tissue.
March 6, 2018: Cell Reports
Alexandre Mayran, Jacques Drouin
Pioneer transcription factors have the unique and important role of unmasking chromatin domains during development to allow the implementation of new cellular programs. Compared to those of other transcription factors, this activity implies that pioneer factors can recognize their target DNA sequences in so-called compacted or "closed" heterochromatin and can trigger remodeling of the adjoining chromatin landscape to provide accessibility to non-pioneer transcription factors. Recent studies identified several steps of pioneer action, namely rapid but weak initial binding to heterochromatin, stabilization of binding followed by chromatin opening and loss of CpG methylation that provides epigenetic memory...
March 5, 2018: Journal of Biological Chemistry
Sweta Srivas, Mahendra K Thakur
Epigenetic modifications through methylation of DNA and acetylation of histones modulate neuronal gene expression and regulate long-term memory. Earlier we demonstrated that scopolamine-induced decrease in memory consolidation is correlated with enhanced expression of hippocampal DNA methyltransferase 1 (DNMT1) and histone deacetylase 2 (HDAC2) in mice. DNMT1 and HDAC2 act together by recruiting a co-repressor complex and deacetylating the chromatin. The catalytic activity of HDACs is mainly dependent on its incorporation into multiprotein co-repressor complexes, among which SIN3A-HDAC2 co-repressor is widely studied to regulate synaptic plasticity...
March 1, 2018: Journal of Neurochemistry
Shusaku Uchida, Gleb P Shumyatsky
Recent evidence demonstrates that epigenetic regulation of gene transcription is critically involved in learning and memory. Here, we discuss the role of histone acetylation and DNA methylation, which are two best understood epigenetic processes in memory processes. More specifically, we focus on learning-strength-dependent changes in chromatin on the fibroblast growth factor 1 (Fgf1) gene and on the molecular events that modulate regulation of Fgf1 transcription, required for memory enhancement, with the specific focus on CREB-regulated transcription coactivator 1 (CRTC1)...
February 22, 2018: Brain Research Bulletin
Keiya Takahashi, Hyun Yi, Ching-Hang Liu, Shue Liu, Yuta Kashiwagi, Dennis J Patin, Shuanglin Hao
The symptoms of HIV-sensory neuropathy are dominated by neuropathic pain. Recent data show that repeated use of opiates enhances the chronic pain states in HIV patients. Limited attention has so far been devoted to exploring the exact pathogenesis of HIV painful disorder and opiate abuse in vivo, for which there is no effective treatment. Bromodomain-containing protein 4 (Brd4) is a member of the bromodomain and extraterminal domain protein (BET) family and functions as a chromatin 'reader' that binds acetylated lysines in histones in brain neurons to mediate the transcriptional regulation underlying learning and memory...
February 20, 2018: Neuroreport
Agnieszka Szymula, Richard D Palermo, Amr Bayoumy, Ian J Groves, Mohammed Ba Abdullah, Beth Holder, Robert E White
The Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) is the first viral latency-associated protein produced after EBV infection of resting B cells. Its role in B cell transformation is poorly defined, but it has been reported to enhance gene activation by the EBV protein EBNA2 in vitro. We generated EBNA-LP knockout (LPKO) EBVs containing a STOP codon within each repeat unit of IR1. EBNA-LP-mutant EBVs established lymphoblastoid cell lines (LCLs) from adult B cells at reduced efficiency, but not from umbilical cord B cells, which died approximately two weeks after infection...
February 20, 2018: PLoS Pathogens
Guanhua Shu, Enikö A Kramár, Alberto J López, Grace Huynh, Marcelo A Wood, Janine L Kwapis
Multiple epigenetic mechanisms, including histone acetylation and nucleosome remodeling, are known to be involved in long-term memory formation. Enhancing histone acetylation by deleting histone deacetylases, like HDAC3, typically enhances long-term memory formation. In contrast, disrupting nucleosome remodeling by blocking the neuron-specific chromatin remodeling subunit BAF53b impairs long-term memory. Here, we show that deleting HDAC3 can ameliorate the impairments in both long-term memory and synaptic plasticity caused by BAF53b mutation...
March 2018: Learning & Memory
Kubra Gulmez Karaca, David V C Brito, Benjamin Zeuch, Ana M M Oliveira
MeCP2 is required both during postnatal neurodevelopment and throughout the adult life for brain function. Although it is well accepted that MeCP2 in the maturing nervous system is critical for establishing normal development, the functions of MeCP2 during adulthood are poorly understood. Particularly, the requirement of hippocampal MeCP2 for cognitive abilities in the adult is not studied. To characterize the role of MeCP2 in adult neuronal function and cognition, we used a temporal and region-specific disruption of MeCP2 expression in the hippocampus of adult male mice...
February 10, 2018: Neurobiology of Learning and Memory
Belinda J Kaskow, Thomas S Buttrick, Hans-Ulrich Klein, Charles White, Justin R Bourgeois, Russell J Ferland, Nikolaos Patsopoulos, Elizabeth M Bradshaw, Philip L De Jager, Wassim Elyaman
Objective: To study the influence of the Abelson helper integration site 1 (AHI1) locus associated with MS susceptibility on CD4+ T cell function. Methods: We characterized the chromatin state of T cells in the MS-associated AHI1 linkage disequilibrium (LD) block. The expression and the role of the AHI1 variant were examined in T cells from genotyped healthy subjects who were recruited from the PhenoGenetic Project, and the function of AHI1 was explored using T cells from Ahi1 knockout mice...
January 2018: Neurology® Neuroimmunology & Neuroinflammation
Amanda N Henning, Rahul Roychoudhuri, Nicholas P Restifo
Upon stimulation, small numbers of naive CD8+ T cells proliferate and differentiate into a variety of memory and effector cell types. CD8+ T cells can persist for years and kill tumour cells and virally infected cells. The functional and phenotypic changes that occur during CD8+ T cell differentiation are well characterized, but the epigenetic states that underlie these changes are incompletely understood. Here, we review the epigenetic processes that direct CD8+ T cell differentiation and function. We focus on epigenetic modification of DNA and associated histones at genes and their regulatory elements...
January 30, 2018: Nature Reviews. Immunology
Alexandre Mayran, Konstantin Khetchoumian, Fadi Hariri, Tomi Pastinen, Yves Gauthier, Aurelio Balsalobre, Jacques Drouin
Pioneer transcription factors establish new cell-fate competence by triggering chromatin remodeling. However, many features of pioneer action, such as their kinetics and stability, remain poorly defined. Here, we show that Pax7, by opening a unique repertoire of enhancers, is necessary and sufficient for specification of one pituitary lineage. Pax7 binds its targeted enhancers rapidly, but chromatin remodeling and gene activation are slower. Enhancers opened by Pax7 show a loss of DNA methylation and acquire stable epigenetic memory, as evidenced by binding of nonpioneer factors after Pax7 withdrawal...
January 22, 2018: Nature Genetics
John N Koberstein, Shane G Poplawski, Mathieu E Wimmer, Giulia Porcari, Charlly Kao, Bruce Gomes, Davide Risso, Hakon Hakonarson, Nancy R Zhang, Robert T Schultz, Ted Abel, Lucia Peixoto
Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder that is associated with genetic risk factors. Most human disease-associated single-nucleotide polymorphisms (SNPs) are not located in genes but rather are in regulatory regions that control gene expression. The function of regulatory regions is determined through epigenetic mechanisms. Parallels between the cellular basis of development and the formation of long-term memory have long been recognized, particularly the role of epigenetic mechanisms in both processes...
January 16, 2018: Science Signaling
Phuc-Loi Luu, Daniela Gerovska, Hans R Schöler, Marcos J Araúzo-Bravo
AIM: Disclosing the mechanisms that regulate reprogramming memory. MATERIALS & METHODS: We established computational procedure to find DNA methylation somatic memory sites (SMSs) at single CpGs and integrated them with genomics, epigenomics, transcriptomics and imprinting information. RESULTS & CONCLUSION: Reprogramming memory persists at late passages in low methylated regions. Contrarily to hypomethylated, hypermethylated SMSs occur at evolutionary conserved sites overlapping active transcription loci in dynamic chromatin regions...
January 16, 2018: Epigenomics
Luigia Pace, Christel Goudot, Elina Zueva, Paul Gueguen, Nina Burgdorf, Joshua J Waterfall, Jean-Pierre Quivy, Geneviève Almouzni, Sebastian Amigorena
After priming, naïve CD8+ T lymphocytes establish specific heritable transcription programs that define progression to long-lasting memory cells or to short-lived effector cells. Although lineage specification is critical for protection, it remains unclear how chromatin dynamics contributes to the control of gene expression programs. We explored the role of gene silencing by the histone methyltransferase Suv39h1. In murine CD8+ T cells activated after Listeria monocytogenes infection, Suv39h1-dependent trimethylation of histone H3 lysine 9 controls the expression of a set of stem cell-related memory genes...
January 12, 2018: Science
Hanah Rodriguez, Assam El-Osta
SIGNIFICANCE: The number of people suffering from diabetes worldwide is steadily rising. Complications from diabetes, including cardiovascular and renal disease, contribute to the high morbidity and mortality associated with this disease. Recent Advances: hyperglycaemia promotes tissue damage through diverse mechanisms involving increased production of reactive oxygen species (ROS). Increased oxidative stress drives changes in chromatin structure that mediate gene expression changes leading to the up-regulation of pro-inflammatory and pro-fibrotic mediators...
January 5, 2018: Antioxidants & Redox Signaling
Yulan Wu, Yi Xu, Xiyao Huang, Danlei Ye, Miaomiao Han, Hui-Li Wang
Lead (Pb) prevails among the environmental hazards against human health. Although increasing evidence highlights the epigenetic roles underlying the Pb-induced neurotoxicity, the exact mechanisms concerning histone acetylation and its causative agents are still at its infancy. In the present study, the roles of histone deacetylases 1 and 2 (HDAC1/2), as well as histone H3 Lys9 acetylation (Ac-H3K9), in Pb-induced neurotoxicity were investigated. Pb was administered to PC12 cells at 10 μM for 24 hours. And Sprague- Dawley rats were chronically exposed to Pb through drinking water containing 250 ppm Pb for 2 months...
January 2, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Giuseppe Sciumè, Han-Yu Shih, Yohei Mikami, John J O'Shea
The discovery of innate lymphoid cells (ILCs) with selective production of cytokines typically attributed to subsets of T helper cells forces immunologists to reassess the mechanisms by which selective effector functions arise. The parallelism between ILCs and T cells extends beyond these two cell types and comprises other innate-like T lymphocytes. Beyond the recognition of specialized effector functionalities in diverse lymphocytes, features typical of T cells, such as plasticity and memory, are also relevant for innate lymphocytes...
2017: Frontiers in Immunology
Xiaobin Zheng, Yixian Zheng
Summary: The genome-wide chromosome conformation capture (Hi-C) has revealed that the eukaryotic genome can be partitioned into A and B compartments that have distinctive chromatin and transcription features. Current Principle Component Analyses (PCA)-based method for the A/B compartment prediction based on Hi-C data requires substantial CPU time and memory. We report the development of a method, CscoreTool, that enables fast and memory-efficient determination of A/B compartments at high resolution even in datasets with low sequencing depth...
December 13, 2017: Bioinformatics
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