Use the keywords feature with a free QxMD account.
Use Read by QxMD to access full text via your institution or open access sources.
Read also provides personalized recommendations to keep you up to date in your field.
Existing User
Sign InNew to Read
Sign Up#1
REVIEW
Abigail V Lee, Kevin A Nestler, Katherine B Chiappinelli
DNA methylation is a critical component of gene regulation and plays an important role in the development of cancer. Hypermethylation of tumor suppressor genes and silencing of DNA repair pathways facilitate uncontrolled cell growth and synergize with oncogenic mutations to perpetuate cancer phenotypes. Additionally, aberrant DNA methylation hinders immune responses crucial for antitumor immunity. Thus, inhibiting dysregulated DNA methylation is a promising cancer therapy. Pharmacologic inhibition of DNA methylation reactivates silenced tumor suppressors and bolster immune responses through induction of viral mimicry...
April 1, 2024: Pharmacology & Therapeutics
#2
Luke T Geiger, Julie-Anne Balouek, Lorna A Farrelly, Andy S Chen, Megan Tang, Shannon N Bennett, Eric J Nestler, Benjamin A Garcia, Ian Maze, Catherine Jensen Peña
Early-life stress increases sensitivity to subsequent stress, which has been observed among humans, other animals, at the level of cellular activity, and at the level of gene expression. However, the molecular mechanisms underlying such long-lasting sensitivity are poorly understood. We tested the hypothesis that persistent changes in transcription and transcriptional potential were maintained at the level of the epigenome, through changes in chromatin. We used a combination of bottom-up mass spectrometry, viral-mediated epigenome-editing, behavioral quantification, and RNA-sequencing in a mouse model of early-life stress, focusing on the ventral tegmental area (VTA), a brain region critically implicated in motivation, reward learning, stress response, and mood and drug disorders...
March 14, 2024: bioRxiv
#3
JOURNAL ARTICLE
Jennifer Blaze, Caleb J Browne, Rita Futamura, Behnam Javidfar, Venetia Zachariou, Eric J Nestler, Schahram Akbarian
DNA cytosine methylation has been documented as a potential epigenetic mechanism of transcriptional regulation underlying opioid use disorder. However, methylation of RNA cytosine residues, which would drive another level of biological influence as an epitranscriptomic mechanism of gene and protein regulation has not been studied in the context of addiction. Here, we probed whether chronic morphine exposure could alter tRNA cytosine methylation (m5 C) and resulting expression levels in the medial prefrontal cortex (mPFC), a brain region crucial for reward processing and executive function that exhibits opioid-induced molecular restructuring...
February 8, 2024: Neuropsychopharmacology
#4
REVIEW
Leanne M Holt, Eric J Nestler
Addiction is a leading cause of disease burden worldwide and remains a challenge in current neuroscience research. Drug-induced lasting changes in gene expression are mediated by transcriptional and epigenetic regulation in the brain and are thought to underlie behavioral adaptations. Emerging evidence implicates astrocytes in regulating drug-seeking behaviors and demonstrates robust transcriptional response to several substances of abuse. This review focuses on the astrocytic transcriptional and epigenetic mechanisms of drug action...
November 8, 2023: Journal of Neural Transmission
#5
JOURNAL ARTICLE
Marion Sourty, Md Taufiq Nasseef, Cédric Champagnol-Di Liberti, Mary Mondino, Vincent Noblet, Eric M Parise, Tamara Markovic, Caleb J Browne, Emmanuel Darcq, Eric J Nestler, Brigitte L Kieffer
BACKGROUND: The transcription factor, ΔFOSB, acting in the nucleus accumbens (NAc), has been shown to control transcriptional and behavioral responses to opioids and other drugs of abuse. However, circuit-level consequences of ΔFOSB induction on the rest of the brain-required for its regulation of complex behavior-remain unknown. METHODS: We used an epigenetic approach in mice to suppress or activate the endogenous Fosb gene, and therefore decrease or increase, respectively, levels of ΔFOSB selectively in D1-type medium spiny neurons of the NAc, and tested whether these modifications affect the organization of functional connectivity (FC) in the brain...
July 28, 2023: Biological Psychiatry
#6
JOURNAL ARTICLE
Szu-Ying Yeh, Molly Estill, Casey K Lardner, Caleb J Browne, Angelica Minier-Toribio, Rita Futamura, Katherine Beach, Catherine A McManus, Song-Jun Xu, Shuo Zhang, Elizabeth A Heller, Li Shen, Eric J Nestler
BACKGROUND: The ability of neurons to respond to external stimuli involves adaptations of gene expression. Induction of the transcription factor ΔFOSB in the nucleus accumbens, a key brain reward region, is important for the development of drug addiction. However, a comprehensive map of ΔFOSB's gene targets has not yet been generated. METHODS: We used CUT&RUN (cleavage under targets and release using nuclease) to map the genome-wide changes in ΔFOSB binding in the 2 main types of nucleus accumbens neurons-D1 or D2 medium spiny neurons-after chronic cocaine exposure...
January 2, 2023: Biological Psychiatry
#7
JOURNAL ARTICLE
Yentl Y van der Zee, Lars M T Eijssen, Philipp Mews, Aarthi Ramakrishnan, Kelvin Alvarez, Casey K Lardner, Hannah M Cates, Deena M Walker, Angélica Torres-Berrío, Caleb J Browne, Ashley Cunningham, Flurin Cathomas, Hope Kronman, Eric M Parise, Laurence de Nijs, Li Shen, James W Murrough, Bart P F Rutten, Eric J Nestler, Orna Issler
Major depressive disorder (MDD) is the leading cause of disability worldwide. There is an urgent need for objective biomarkers to diagnose this highly heterogeneous syndrome, assign treatment, and evaluate treatment response and prognosis. MicroRNAs (miRNAs) are short non-coding RNAs, which are detected in body fluids that have emerged as potential biomarkers of many disease conditions. The present study explored the potential use of miRNAs as biomarkers for MDD and its treatment. We profiled the expression levels of circulating blood miRNAs from mice that were collected before and after exposure to chronic social defeat stress (CSDS), an extensively validated mouse model used to study depression, as well as after either repeated imipramine or single-dose ketamine treatment...
July 28, 2022: Molecular Psychiatry
#8
JOURNAL ARTICLE
Kerri D Pryce, Aarthi Ramakrishnan, Hope Kronnman, Andrew Nicolais, Claire Polizu, Anne Ruiz, Randal Serafini, Sevasti Gaspari, Catherine J Pena, Angelica Torres-Berrio, Vassiliki Mitsi, Matthew Darpe, L I Shen, Eric J Nestler, Venetia Zachariou
The development of physical dependence and addiction disorders due to misuse of opioid analgesics is a major concern with pain therapeutics. In this study, we developed a mouse model of oxycodone misuse in order to gain insight into genes and molecular pathways in reward-related brain regions that are affected by prolonged exposure to oxycodone and subsequent withdrawal in the presence or absence of chronic neuropathic pain. RNA-sequencing (RNA-seq) and bioinformatic analyses revealed that oxycodone withdrawal alone triggers robust gene expression adaptations in the nucleus accumbens (NAc), medial prefrontal cortex (mPFC), and ventral tegmental area (VTA), with numerous genes and pathways selectively affected by oxycodone withdrawal under peripheral nerve injury states...
May 2022: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
#9
REVIEW
Collin D Teague, Eric J Nestler
Targeted epigenetic remodeling in the rat amygdala reverses the effects of adolescent alcohol consumption on excessive drinking and anxiety-like behavior in adulthood.
May 6, 2022: Science Advances
#10
JOURNAL ARTICLE
Lu Wang, Noah Warren Birch, Zibo Zhao, Carson Meredith Nestler, Alexander Kazmer, Anthony Shilati, Alisha Blake, Patrick Alexander Ozark, Emily Jane Rendleman, Didi Zha, Caila Ann Ryan, Marc Alard Jonathan Morgan, Ali Shilatifard
Mutations of ASXL1, encoding a component of the BAP1 histone H2A deubiquitinase complex, occur in human myeloid neoplasms and are uniformly associated with poor prognosis. However, the precise molecular mechanisms through which ASXL1 mutations alter BAP1 activity and drive leukemogenesis remain unclear. Here we demonstrate that cancer-associated frameshift mutations in ASXL1, which were originally proposed to act as destabilizing loss-of-function mutations, in fact encode stable truncated gain-of-function proteins...
May 2021: Nature Cancer
#11
JOURNAL ARTICLE
Benjamin Valentin Becker, Hanns Leonhard Kaatsch, Kai Nestler, Julia Jakobi, Barbara Schäfer, Thomas Hantke, Marc A Brockmann, Stephan Waldeck, Matthias Port, Reinhard Ullmann
BACKGROUND: Computed tomography (CT) is a main contributor to artificial low-dose exposure. Understanding the biological effects induced by CT exposure and their dependency on the characteristics of photon spectra is essential for knowledge-driven risk assessment. In a previous gene expression study, we have identified upregulation of AEN , BAX , DDB2, EDA2R and FDXR after ex vivo exposure with single- and dual-energy CT. In this study, we focused on CT-induced changes of DNA methylation...
November 15, 2021: International Journal of Radiation Biology
#12
JOURNAL ARTICLE
Kathryn Vaillancourt, Gang G Chen, Laura Fiori, Gilles Maussion, Volodymyr Yerko, Jean-François Théroux, Carl Ernst, Benoit Labonté, Erin Calipari, Eric J Nestler, Corina Nagy, Naguib Mechawar, Deborah C Mash, Gustavo Turecki
Cocaine dependence is a chronic, relapsing disorder caused by lasting changes in the brain. Animal studies have identified cocaine-related alterations in striatal DNA methylation; however, it is unclear how methylation is related to cocaine dependence in humans. We generated methylomic profiles of the nucleus accumbens using human postmortem brains from a cohort of individuals with cocaine dependence and healthy controls (n = 25 per group). We found hypermethylation in a cluster of CpGs within the gene body of tyrosine hydroxylase (TH), containing a putative binding site for the early growth response 1 (EGR1) transcription factor, which is hypermethylated in the caudate nucleus of cocaine-dependent individuals...
October 22, 2021: IScience
#13
JOURNAL ARTICLE
Ashley M Cunningham, Deena M Walker, Aarthi Ramakrishnan, Marie A Doyle, Rosemary C Bagot, Hannah M Cates, Catherine J Peña, Orna Issler, Casey Lardner, Caleb Browne, Scott J Russo, Li Shen, Eric J Nestler
Paternal stress can induce long-lasting changes in germ cells potentially propagating heritable changes across generations. To date, no studies have investigated differences in transmission patterns between stress-resilient and -susceptible mice. We tested the hypothesis that transcriptional alterations in sperm during chronic social defeat stress (CSDS) transmit increased susceptibility to stress phenotypes to the next generation. We demonstrate differences in offspring from stressed fathers that depend upon paternal category (resilient vs susceptible) and offspring sex...
June 7, 2021: Journal of Neuroscience
#14
REVIEW
Rohan H C Palmer, Emma C Johnson, Hyejung Won, Renato Polimanti, Manav Kapoor, Apurva Chitre, Molly A Bogue, Chelsie E Benca-Bachman, Clarissa C Parker, Oana Ursu, Anurag Verma, Timothy Reynolds, Jason Ernst, Michael Bray, Soo Bin Kwon, Dongbing Lai, Bryan C Quach, Nathan C Gaddis, Laura Saba, Hao Chen, Michael Hawrylycz, Shan Zhang, Yuan Zhou, Spencer Mahaffey, Christian Fischer, Sandra Sanchez-Roige, Anita Bandrowski, Lu Qing, Li Shen, Vivek Philip, Joel Gelernter, Laura J Bierut, Dana B Hancock, Howard J Edenberg, Eric O Johnson, Eric J Nestler, Peter B Barr, Pjotr Prins, Desmond J Smith, Schahram Akbarian, Thorgeir Thorgeirsson, Dave Walton, Erich Baker, Daniel Jacobson, Abraham A Palmer, Michael Miles, Elissa J Chesler, Jake Emerson, Arpana Agrawal, Maryann Martone, Robert W Williams
The National Institute on Drug Abuse and Joint Institute for Biological Sciences at the Oak Ridge National Laboratory hosted a meeting attended by a diverse group of scientists with expertise in substance use disorders (SUDs), computational biology, and FAIR (Findability, Accessibility, Interoperability, and Reusability) data sharing. The meeting's objective was to discuss and evaluate better strategies to integrate genetic, epigenetic, and 'omics data across human and model organisms to achieve deeper mechanistic insight into SUDs...
April 23, 2021: Genes, Brain, and Behavior
#15
JOURNAL ARTICLE
Hope Kronman, Angélica Torres-Berrío, Simone Sidoli, Orna Issler, Arthur Godino, Aarthi Ramakrishnan, Philipp Mews, Casey K Lardner, Eric M Parise, Deena M Walker, Yentl Y van der Zee, Caleb J Browne, Brittany F Boyce, Rachael Neve, Benjamin A Garcia, Li Shen, Catherine J Peña, Eric J Nestler
Animals susceptible to chronic social defeat stress (CSDS) exhibit depression-related behaviors, with aberrant transcription across several limbic brain regions, most notably in the nucleus accumbens (NAc). Early life stress (ELS) promotes susceptibility to CSDS in adulthood, but associated enduring changes in transcriptional control mechanisms in the NAc have not yet been investigated. In this study, we examined long-lasting changes to histone modifications in the NAc of male and female mice exposed to ELS...
May 2021: Nature Neuroscience
#16
JOURNAL ARTICLE
Kathryn Vaillancourt, Jennie Yang, Gary G Chen, Volodymyr Yerko, Jean-François Théroux, Zahia Aouabed, Alberto Lopez, Kimberly C Thibeault, Erin S Calipari, Benoit Labonté, Naguib Mechawar, Carl Ernst, Corina Nagy, Thierry Forné, Eric J Nestler, Deborah C Mash, Gustavo Turecki
Epigenetic mechanisms, like those involving DNA methylation, are thought to mediate the relationship between chronic cocaine dependence and molecular changes in addiction-related neurocircuitry, but have been understudied in human brain. We initially used reduced representation bisulfite sequencing (RRBS) to generate a methylome-wide profile of cocaine dependence in human post-mortem caudate tissue. We focused on the Iroquois Homeobox A (IRXA) gene cluster, where hypomethylation in exon 3 of IRX2 in neuronal nuclei was associated with cocaine dependence...
July 2021: Molecular Psychiatry
#17
REVIEW
Yun Young Yim, Collin D Teague, Eric J Nestler
Studies over the past several decades have identified numerous epigenetic mechanisms associated with pathological states in psychiatric and neurological disease. Until recently, studies investigating chromatin-regulatory proteins, using overexpression or knockdown approaches, did not establish causal roles for epigenetic modifications at specific genes because these techniques typically affect hundreds or thousands of genomic loci. In this Review, we describe recent efforts in using locus-specific neuroepigenome editing in vivo to, for the first time, define causal relationships between a single chromatin modification at a specific gene in a defined cell population and downstream measures at the molecular, cellular, circuit and behavioural levels...
September 2020: Nature Reviews. Neuroscience
#18
JOURNAL ARTICLE
Angélica Torres-Berrío, Orna Issler, Eric M Parise, Eric J Nestler
Depression is a devastating psychiatric disorder caused by a combination of genetic predisposition and life events, mainly exposure to stress. Early life stress (ELS) in particular is known to "scar" the brain, leading to an increased susceptibility to developing depression later in life via epigenetic mechanisms. Epigenetic processes lead to changes in gene expression that are not due to changes in DNA sequence, but achieved via modulation of chromatin modifications, DNA methylation, and noncoding RNAs...
December 2019: Dialogues in Clinical Neuroscience
#19
JOURNAL ARTICLE
Benoit Labonté, Khaled Abdallah, Gilles Maussion, Volodymyr Yerko, Jennie Yang, Thibault Bittar, Francis Quessy, Sam A Golden, Luis Navarro, Dave Checknita, Carolina Gigek, Juan Pablo Lopez, Rachael L Neve, Scott J Russo, Richard E Tremblay, Gilles Côté, Michael J Meaney, Naguib Mechawar, Eric J Nestler, Gustavo Turecki
High impulsive and aggressive traits associate with poor behavioural self-control. Despite their importance in predicting behavioural negative outcomes including suicide, the molecular mechanisms underlying the expression of impulsive and aggressive traits remain poorly understood. Here, we identified and characterized a novel long noncoding RNA (lncRNA), acting as a regulator of the monoamine oxidase A (MAOA) gene in the brain, and named it MAOA-associated lncRNA (MAALIN). Our results show that in the brain of suicide completers, MAALIN is regulated by a combination of epigenetic mechanisms including DNA methylation and chromatin modifications...
January 6, 2020: Molecular Psychiatry
#20
JOURNAL ARTICLE
P Mews, G Egervari, R Nativio, S Sidoli, G Donahue, S I Lombroso, D C Alexander, S L Riesche, E A Heller, E J Nestler, B A Garcia, S L Berger
Emerging evidence suggests that epigenetic regulation is dependent on metabolic state, and implicates specific metabolic factors in neural functions that drive behaviour1 . In neurons, acetylation of histones relies on the metabolite acetyl-CoA, which is produced from acetate by chromatin-bound acetyl-CoA synthetase 2 (ACSS2)2 . Notably, the breakdown of alcohol in the liver leads to a rapid increase in levels of blood acetate3 , and alcohol is therefore a major source of acetate in the body. Histone acetylation in neurons may thus be under the influence of acetate that is derived from alcohol4 , with potential effects on alcohol-induced gene expression in the brain, and on behaviour5 ...
October 2019: Nature
Make the most of Read.
Download the mobile app.
Download the mobile app.
Fetching more papers... 
