Protein monoaminylation is a biochemical process through which biogenic monoamines (e.g., serotonin, dopamine, histamine, etc.) are covalently bonded to certain protein substrates via ...Transglutaminase 2, an enzyme that catalyzes the transamidation of primary amines to the γ-carboxamides of glutamine residues. Since their initial discovery, these unusual post-translational modifications have been implicated in a wide variety of biological processes, ranging from protein coagulation to platelet activation and G-protein signaling. More recently, histone proteins – specifically histone H3 at glutamine 5 (H3Q5) – have been added to the growing list of monoaminyl substrates in vivo, with H3Q5 monoaminylation demonstrated to regulate permissive gene expression in cells. Such phenomena have further been shown to contribute critically to various aspects of (mal)adaptive neuronal plasticity and behavior. In this short review, we examine the evolution of our understanding of protein monoaminylation events, highlighting recent advances in the elucidation of their roles as important chromatin regulators.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Ethanol consumption produces characteristic behavioral states in animals that include sedation, disorientation, and disruption of motor function. Using individual honey bees, we assessed the effects ...of ethanol ingestion on motor function via continuous observations of their behavior. Consumption of 1
M sucrose solutions containing a range of ethanol doses led to hemolymph ethanol levels of approximately 40–100
mM. Using ethanol doses in this range, we observed time and dose-dependent effects of ethanol on the percent of time our subjects spent walking, stopped, or upside down, and on the duration and frequency of bouts of behavior. The effects on grooming and flying behavior were more complex. Behavioral recovery from ethanol treatment was both time and ethanol dose dependent, occurring between 12 and 24
h post-ingestion for low doses and at 24–48
h for higher doses. Furthermore, the amount of ethanol measured in honey bee hemolymph appeared to correlate with recovery. We predict that the honey bee will prove to be an excellent model system for studying the influence of ethanol on the neural mechanisms underlying behavior.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
•Histone regulation in brain is a central determinant of neural development and plasticity.•Many neurological diseases are linked to aberrant histone regulation in the CNS.•New methods for ...investigating histones may help to causally link them to biological function.
The last two decades have witnessed explosive advances in our understanding as to how the organization of chromatin, the association of DNA with histones and vast numbers of non-histone regulatory proteins, controls the expression of specific genes in brain. Prominent among such regulatory mechanisms are modifications of histones, along with the ‘writers,’ ‘erasers,’ and ‘readers’ of these modifications. Much of the work delineating these mechanisms has contributed to the idea that a ‘histone code’ may be a central determinant of a gene’s activity and its potential to be activated or repressed in response to environmental perturbations (both beneficial and aberrant). Indeed, increasing evidence has demonstrated the significance of histone regulation in neurological plasticity and disease, although we are still at the earliest stages of examining all of the many potential chromatin changes involved. In this short review, we provide an emerging perspective on putative roles for histones, and their combinatorial readouts, in the context of neural plasticity, and we provide a conceptual framework for future mechanistic studies aimed at uncovering causal links between the neural ‘histone code’ and brain function/disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Postmitotic neurons are subject to a vast array of environmental influences that require the nuclear integration of intracellular signaling events to promote a wide variety of neuroplastic states ...associated with synaptic function, circuit formation, and behavioral memory. Over the last decade, much attention has been paid to the roles of transcription and chromatin regulation in guiding fundamental aspects of neuronal function. A great deal of this work has centered on neurodevelopmental and adulthood plasticity, with increased focus in the areas of neuropharmacology and molecular psychiatry. Here, we attempt to provide a broad overview of chromatin regulation, as it relates to central nervous system (CNS) function, with specific emphasis on the modes of histone posttranslational modifications, chromatin remodeling, and histone variant exchange. Understanding the functions of chromatin in the context of the CNS will aid in the future development of pharmacological therapeutics aimed at alleviating devastating neurological disorders.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Chemical modifications of histones can mediate diverse DNA-templated processes, including gene transcription
. Here we provide evidence for a class of histone post-translational modification, ...serotonylation of glutamine, which occurs at position 5 (Q5ser) on histone H3 in organisms that produce serotonin (also known as 5-hydroxytryptamine (5-HT)). We demonstrate that tissue transglutaminase 2 can serotonylate histone H3 tri-methylated lysine 4 (H3K4me3)-marked nucleosomes, resulting in the presence of combinatorial H3K4me3Q5ser in vivo. H3K4me3Q5ser displays a ubiquitous pattern of tissue expression in mammals, with enrichment observed in brain and gut, two organ systems responsible for the bulk of 5-HT production. Genome-wide analyses of human serotonergic neurons, developing mouse brain and cultured serotonergic cells indicate that H3K4me3Q5ser nucleosomes are enriched in euchromatin, are sensitive to cellular differentiation and correlate with permissive gene expression, phenomena that are linked to the potentiation of TFIID
interactions with H3K4me3. Cells that ectopically express a H3 mutant that cannot be serotonylated display significantly altered expression of H3K4me3Q5ser-target loci, which leads to deficits in differentiation. Taken together, these data identify a direct role for 5-HT, independent from its contributions to neurotransmission and cellular signalling, in the mediation of permissive gene expression.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Epigenetics of Drug Addiction Stewart, Andrew F; Fulton, Sasha L; Maze, Ian
Cold Spring Harbor perspectives in medicine,
07/2021, Volume:
11, Issue:
7
Journal Article
Peer reviewed
Open access
Substance use disorders (SUDs) are chronic brain diseases characterized by transitions from recreational to compulsive drug use and aberrant drug craving that persists for months to years after ...abstinence is achieved. The transition to compulsive drug use implies that plasticity is occurring, altering the physiology of the brain to precipitate addicted states. Epigenetic phenomena represent a varied orchestra of transcriptional tuning mechanisms that, in response to environmental stimuli, create and maintain gene expression-mediated physiological outcomes. Therefore, epigenetic mechanisms represent a convergent regulatory framework through which the plasticity required to achieve an addicted state can arise and then persist long after drug use has ended. In the first section, we will introduce basic concepts in epigenetics, such as chromatin architecture, histones and their posttranslational modifications, DNA methylation, noncoding RNAs, and transcription factors, along with methods for their investigation. We will then examine the implications of these mechanisms in SUDs, with a particular focus on cocaine-mediated neuroepigenetic plasticity across multiple behavioral models of addiction.
Highlights • We studied histone acetylation in the medial prefrontal cortex in stress models. • Chronic social stress increased histone acetylation levels in the prefrontal cortex. • Chronic ...fluoxetine had no effect on histone acetylation in the prefrontal cortex. • Histone deacetylase inhibition in the prefrontal cortex was antidepressant-like. • The data support the evaluation of histone deacetylase inhibitors as antidepressants.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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