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Peter J Hamilton, Carissa J Lim, Eric J Nestler, Elizabeth A Heller
Delivery of molecular tools for targeted epigenome editing in rodent brain can be facilitated by the use of viral vector-mediated gene transfer coupled with stereotaxic surgery techniques. Here, we describe the surgical protocol utilized by our group, which is optimized for herpes simplex virus (HSV)-mediated delivery into mouse brain. The protocol outlined herein could also be applied for delivery of adeno-associated viruses (AAV) or lentiviruses in both mice and rats. This method allows for efficient viral transgene expression and subsequent epigenome editing in rodent brain with excellent spatiotemporal control...
2018: Methods in Molecular Biology
Ariel Cariaga-Martinez, Raúl Alelú-Paz
Schizophrenia is a complex mental disorder whose causes are still far from being known. Although researchers have focused on genetic or environmental contributions to the disease, we still lack a scientific framework that joins molecular and clinical findings. Epigenetic can explain how environmental variables may affect gene expression without modifying the DNA sequence. In fact, neuroepigenomics represents an effort to unify the research available on the molecular pathology of mental diseases, which has been carried out through several approaches ranging from interrogating single DNA methylation events and hydroxymethylation patterns, to epigenome-wide association studies, as well as studying post-translational modifications of histones, or nucleosomal positioning...
April 7, 2017: International Journal of Molecular Sciences
John F Fullard, Tobias B Halene, Claudia Giambartolomei, Vahram Haroutunian, Schahram Akbarian, Panos Roussos
The Psychiatric Genomics Consortium-Schizophrenia Workgroup (PGC-SCZ) recently identified 108 loci associated with increased risk for schizophrenia (SCZ). The vast majority of these variants reside within non-coding sequences of the genome and are predicted to exert their effects by affecting the mechanism of action of cis regulatory elements (CREs), such as promoters and enhancers. Although a number of large-scale collaborative efforts (e.g. ENCODE) have achieved a comprehensive mapping of CREs in human cell lines or tissue homogenates, it is becoming increasingly evident that many risk-associated variants are enriched for expression Quantitative Trait Loci (eQTLs) and CREs in specific tissues or cells...
November 2016: Schizophrenia Research
John S Satterlee, Andrea Beckel-Mitchener, Roger Little, Dena Procaccini, Joni L Rutter, Amy C Lossie
Long-lived post-mitotic cells, such as the majority of human neurons, must respond effectively to ongoing changes in neuronal stimulation or microenvironmental cues through transcriptional and epigenomic regulation of gene expression. The role of epigenomic regulation in neuronal function is of fundamental interest to the neuroscience community, as these types of studies have transformed our understanding of gene regulation in post-mitotic cells. This perspective article highlights many of the resources available to researchers interested in neuroepigenomic investigations and discusses some of the current obstacles and opportunities in neuroepigenomics...
January 1, 2015: Neuroepigenetics
Ian Maze, Li Shen, Bin Zhang, Benjamin A Garcia, Ningyi Shao, Amanda Mitchell, HaoSheng Sun, Schahram Akbarian, C David Allis, Eric J Nestler
Over the past decade, rapid advances in epigenomics research have extensively characterized critical roles for chromatin regulatory events during normal periods of eukaryotic cell development and plasticity, as well as part of aberrant processes implicated in human disease. Application of such approaches to studies of the CNS, however, is more recent. Here we provide a comprehensive overview of available tools for analyzing neuroepigenomics data, as well as a discussion of pending challenges specific to the field of neuroscience...
November 2014: Nature Neuroscience
Lucio Tremolizzo, Virginia Rodriguez-Menendez, Elisa Conti, Chiara Paola Zoia, Guido Cavaletti, Carlo Ferrarese
The neuroepigenome, i.e., the epigenome of the nervous system, has become interesting for therapeutics in the last years due to widespread availability of dedicated drugs. A pivotal role for neuroepigenetics is certainly implied, both in physiology and pathology, by the highly dynamic structural and functional rearrangements that constantly occur into the nervous system, globally known as plasticity. Moreover, the idea that the pathophysiology of several neuropsychiatric disorders might involve epigenetic mechanisms is increasingly taking place due to accumulating experimental data and by the evidence of a synergistic interaction between genes and environment beneath most sporadic forms of these diseases...
2014: Current Pharmaceutical Design
Andrew S McLellan, Robert A Dubin, Qiang Jing, Shahina B Maqbool, Raul Olea, Gael Westby, Pilib Ó Broin, Melissa J Fazzari, Deyou Zheng, Masako Suzuki, John M Greally
There is increasing interest in the role of epigenetic and transcriptional dysregulation in the pathogenesis of a range of human diseases, not just in the best-studied example of cancer. It is, however, quite difficult for an individual investigator to perform these studies, as they involve genome-wide molecular assays combined with sophisticated computational analytical approaches of very large datasets that may be generated from various resources and technologies. In 2008, the Albert Einstein College of Medicine in New York, USA established a Center for Epigenomics to facilitate the research programs of its investigators, providing shared resources for genome-wide assays and for data analysis...
October 2009: Epigenomics
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