Retinal gene expression shows compartment specific differences in health and disease

The biopsychosocial (BPS) model of psychiatry has had a major impact on our modern conceptualization of mental illness as a complex, multi-determined phenomenon. Yet, interdisciplinary BPS work remains the exception, rather than the rule in psychiatry. It has been suggested that this may stem in part from a failure of the BPS model to clearly delineate the mechanisms through which biological, psychological, and social factors co-act in the development of mental illness. This chapter discusses how epigenetic processes that regulate gene expression, such as DNA methylation, are fast emerging as a candidate mechanism for BPS interactions, with potentially widespread implications for the way that psychiatric disorders are understood, assessed, and, perhaps in future, even treated.

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Dietary microRNA—A Novel Functional Component of Food

Advances in Nutrition ◽

10.1093/advances/nmy127 ◽

2019 ◽

Vol 10 (4) ◽

pp. 711-721 ◽

Cited By ~ 8

Author(s):

Lin Zhang ◽

Ting Chen ◽

Yulong Yin ◽

Chen-Yu Zhang ◽

Yong-Liang Zhang

Keyword(s):

Gene Expression ◽

Small Rnas ◽

Biological Significance ◽

Circulatory System ◽

Physiological Effects ◽

Biological Processes ◽

Regulate Gene Expression ◽

Functional Component ◽

Health And Disease ◽

Regulate Gene

ABSTRACT MicroRNAs are a class of small RNAs that play essential roles in various biological processes by silencing genes. Evidence emerging in recent years suggests that microRNAs in food can be absorbed into the circulatory system and organs of humans and other animals, where they regulate gene expression and biological processes. These food-derived dietary microRNAs may serve as a novel functional component of food, a role that has been neglected to date. However, a significant amount of evidence challenges this new concept. The absorption, stability, and physiological effects of dietary microRNA in recipients, especially in mammals, are currently under heavy debate. In this review, we summarize our current understanding of the unique characteristics of dietary microRNAs and concerns about both the mechanistic and methodological basis for studying the biological significance of dietary microRNAs. Such efforts will benefit continuing investigations and offer new perspectives for the interpretation of the roles of dietary microRNA with respect to the health and disease of humans and animals.

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The role of vitamins and minerals in modulating the expression of microRNA

Nutrition Research Reviews ◽

10.1017/s0954422414000043 ◽

2014 ◽

Vol 27 (1) ◽

pp. 94-106 ◽

Cited By ~ 23

Author(s):

Emma L. Beckett ◽

Zoe Yates ◽

Martin Veysey ◽

Konsta Duesing ◽

Mark Lucock

Keyword(s):

Gene Expression ◽

Food Sources ◽

Transcriptional Level ◽

Disease States ◽

Regulatory Circuit ◽

Non Coding Rna ◽

Epigenetic Machinery ◽

Health And Disease ◽

Expression Potential

A growing number of studies in recent years have highlighted the importance of molecular nutrition as a potential determinant of health and disease. In particular, the ability of micronutrients to regulate the final expression of gene products via modulation of transcription and translation is now being recognised. Modulation of microRNA (miRNA) by nutrients is one pathway by which nutrition may mediate gene expression. miRNA, a class of non-coding RNA, can directly regulate gene expression post-transcriptionally. In addition, miRNA are able to indirectly influence gene expression potential at the transcriptional level via modulation of the function of components of the epigenetic machinery (DNA methylation and histone modifications). These mechanisms interact to form a complex, bi-directional regulatory circuit modulating gene expression. Disease-specific miRNA profiles have been identified in multiple disease states, including those with known dietary risk factors. Therefore, the role that nutritional components, in particular, vitamins and minerals, play in the modulation of miRNA profiles, and consequently health and disease, is increasingly being investigated, and as such is a timely subject for review. The recently posited potential for viable exogenous miRNA to enter human blood circulation from food sources adds another interesting dimension to the potential for dietary miRNA to contribute to gene modulation.

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Glucocorticoid receptor action in metabolic and neuronal function

F1000Research ◽

10.12688/f1000research.11375.1 ◽

2017 ◽

Vol 6 ◽

pp. 1208 ◽

Cited By ~ 19

Author(s):

Michael J. Garabedian ◽

Charles A. Harris ◽

Freddy Jeanneteau

Keyword(s):

Gene Expression ◽

Glucocorticoid Receptor ◽

Metabolic Diseases ◽

Cell Types ◽

Health And Disease ◽

And Behavior ◽

External Signals ◽

The Brain

Glucocorticoids via the glucocorticoid receptor (GR) have effects on a variety of cell types, eliciting important physiological responses via changes in gene expression and signaling. Although decades of research have illuminated the mechanism of how this important steroid receptor controls gene expression using in vitro and cell culture–based approaches, how GR responds to changes in external signals in vivo under normal and pathological conditions remains elusive. The goal of this review is to highlight recent work on GR action in fat cells and liver to affect metabolism in vivo and the role GR ligands and receptor phosphorylation play in calibrating signaling outputs by GR in the brain in health and disease. We also suggest that both the brain and fat tissue communicate to affect physiology and behavior and that understanding this “brain-fat axis” will enable a more complete understanding of metabolic diseases and inform new ways to target them.

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Omega-3 Fatty Acids in Health and Disease: Part 2—Health Effects of Omega-3 Fatty Acids in Autoimmune Diseases, Mental Health, and Gene Expression

Journal of Medicinal Food ◽

10.1089/jmf.2005.8.133 ◽

2005 ◽

Vol 8 (2) ◽

pp. 133-148 ◽

Cited By ~ 54

Author(s):

Fereidoon Shahidi ◽

Homan Miraliakbari

Keyword(s):

Gene Expression ◽

Mental Health ◽

Fatty Acids ◽

Autoimmune Diseases ◽

Health Effects ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

Health And Disease

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Genetic control of global gene expression levels in the intestinal mucosa: a human twin study

Physiological Genomics ◽

10.1152/physiolgenomics.00010.2009 ◽

2009 ◽

Vol 38 (1) ◽

pp. 73-79 ◽

Cited By ~ 13

Author(s):

Robert Häsler ◽

Alexander Begun ◽

Sandra Freitag-Wolf ◽

Martin Kerick ◽

Nancy Mah ◽

...

Keyword(s):

Gene Expression ◽

Mrna Expression ◽

Genetic Control ◽

Intestinal Mucosa ◽

Expression Profiles ◽

Global Gene Expression ◽

Model Organisms ◽

Expression Levels ◽

Molecular Phylogenetic ◽

Health And Disease

Phenotypic variation between individuals, such as different mRNA expression levels, is influenced by genetic and nongenetic factors. Although several studies have addressed the interplay between genotypes and expression profiles in various model organisms in the recent years, the detailed and relative contributions of genetic and nongenetic factors in regulating plasticity of gene expression in barrier organs (e.g., skin, gut), which are exposed to continuous environmental challenge, are still poorly understood. Here we systematically monitored the level of genetic control over genomewide mRNA expression profiles in the healthy intestinal mucosa of 10 monozygotic and 10 dizygotic human twin pairs with microarray analyses. Our results, which are supported by real-time PCR and analysis of molecular phylogenetic conservation, indicate that genes associated with energy metabolism and cell and tissue regeneration pathways are under strong genetic control. Conversely, genes associated with immune response seem to be mainly controlled by exogenous factors. Further insights into the relative extent of genetic and nongenetic determinants of transcriptomal profiles and their influence on physiological and pathophysiological mechanisms are crucial to understanding the key role played by gene-environment interactions in health and disease.

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An improved CRISPR/dCas9 interference tool for neuronal gene suppression

10.1101/2020.05.26.116822 ◽

2020 ◽

Author(s):

Corey G. Duke ◽

Svitlana V. Bach ◽

Jasmin S. Revanna ◽

Faraz A. Sultan ◽

Nicholas T. Southern ◽

...

Keyword(s):

Gene Expression ◽

Transcriptional Repression ◽

Expression System ◽

Genetic Material ◽

Gene Promoters ◽

Disease States ◽

Transcriptional Inhibition ◽

Health And Disease ◽

Neuronal Systems ◽

And Function

The expression of genetic material governs brain development, differentiation, and function, and targeted manipulation of gene expression is required to understand contributions of gene function to health and disease states. Although recent improvements in CRISPR/dCas9 interference (CRISPRi) technology have enabled targeted transcriptional repression at selected genomic sites, integrating these techniques for use in non-dividing neuronal systems remains challenging. Previously, we optimized a dual lentivirus expression system to express CRISPR-based activation machinery in post-mitotic neurons. Here we used a similar strategy to adapt an improved dCas9-KRAB-MeCP2 repression system for robust transcriptional inhibition in neurons. We find that lentiviral delivery of a dCas9-KRAB-MeCP2 construct driven by the neuron-selective promoter human synapsin 1 enabled transgene expression in primary rat neurons. Next, we demonstrate transcriptional repression using CRISPR sgRNAs targeting diverse gene promoters, and show superiority of this system in neurons compared to existing RNA interference methods for robust transcript specific manipulation at the complex Brain-derived neurotrophic factor (Bdnf) gene. Our findings advance this improved CRISPRi technology for use in neuronal systems for the first time, potentially enabling improved ability to manipulate gene expression states in the nervous system.

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