Post-translational modifications of histone proteins by monoamine neurotransmitters

Al-Kachak, Amni; Maze, Ian

doi:10.1016/j.cbpa.2023.102302

Cited by 10 publications

(11 citation statements)

References 40 publications

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“…In addition to its role as a neuromodulator, 5-HT was previously shown to be capable of forming covalent bonds with certain substrate proteins via transamidation by the tissue Transglutaminase 2 enzyme, a process referred to as serotonylation (17). In more recent studies, our group identified a new class of histone posttranslational modification (PTM) termed monoaminylation, whereby monoamine neurotransmitters, such as 5-HT, dopamine and histamine, can be transamidated onto histone glutamine residues (18)(19)(20)(21)(22)(23). We showed that histone H3 glutamine (Q) 5 is a primary site for these PTMs and demonstrated that H3 monoaminylation states play important roles in the regulation of neuronal transcriptional programs, both during early development/cellular differentiation and in adult brain.…”

Section: Introductionmentioning

confidence: 99%

Histone H3 serotonylation dynamics in dorsal raphe nucleus contribute to stress- and antidepressant-mediated gene expression and behavior

Al-Kachak

Fulton

Farrelly

et al. 2023

Preprint

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Background: Major depressive disorder (MDD) is a debilitating illness that affects millions of individuals worldwide. While chronic stress increases incidence levels of MDD, stress-mediated disruptions in brain function that precipitate the disorder remain elusive. Serotonin-associated antidepressants (ADs) remain the first line of therapy for many with MDD, yet low remission rates and delays between treatment and symptomatic alleviation have prompted skepticism regarding precise roles for serotonin in the precipitation of MDD. Our group recently demonstrated that serotonin epigenetically modifies histone proteins (H3K4me3Q5ser) to regulate transcriptional permissiveness in brain. However, this phenomenon has not yet been explored following stress and/or AD exposures. Methods: Here, we employed a combination of genome-wide (ChIP-seq, RNA-seq) and western blotting analyses in dorsal raphe nucleus (DRN) of male and female mice exposed to chronic social defeat stress to examine the impact of stress exposures on H3K4me3Q5ser dynamics in DRN, as well as associations between the mark and stress-induced gene expression. Stress-induced regulation of H3K4me3Q5ser levels were also assessed in the context of AD exposures, and viral-mediated gene therapy was employed to manipulate H3K4me3Q5ser levels to examine the impact of reducing the mark in DRN on stress-associated gene expression and behavior. Results: We found that H3K4me3Q5ser plays important roles in stress-mediated transcriptional plasticity in DRN. Mice exposed to chronic stress displayed dysregulated dynamics of H3K4me3Q5ser in DRN, and viral-mediated attenuation of these dynamics rescued stress-mediated gene expression programs and behavior. Conclusions: These findings establish a neurotransmission-independent role for serotonin in stress-associated transcriptional and behavioral plasticity in DRN.

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Section: Introductionmentioning

confidence: 99%

Histone H3 serotonylation dynamics in dorsal raphe nucleus contribute to stress- and antidepressant-mediated gene expression and behavior

Al-Kachak

Fulton

Farrelly

et al. 2023

Preprint

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“…are covalently linked to glutamine residues within certain protein substrates, by Transglutaminase 2, an enzyme that catalyzes the transamidation reaction of primary amines to glutamine-carboxamides ( 126 ). Monoaminylation is important in several aspects of cellular plasticity (in the brain and maybe elsewhere) ( 127 ). Because monoaminylation is one of numerous newly found histone PTMs, further studies are ongoing that may have biological significance in terms of carcinogenesis and cancer therapy.…”

Section: Novel Post-translational Modificationsmentioning

confidence: 99%

Post-translational modifications and their implications in cancer

Dutta,

Jain

2023

Front. Oncol.

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Post-translational modifications (PTMs) are crucial regulatory mechanisms that alter the properties of a protein by covalently attaching a modified chemical group to some of its amino acid residues. PTMs modulate essential physiological processes such as signal transduction, metabolism, protein localization, and turnover and have clinical relevance in cancer and age-related pathologies. Majority of proteins undergo post-translational modifications, irrespective of their occurrence in or after protein biosynthesis. Post-translational modifications link to amino acid termini or side chains, causing the protein backbone to get cleaved, spliced, or cyclized, to name a few. These chemical modifications expand the diversity of the proteome and regulate protein activity, structure, locations, functions, and protein-protein interactions (PPIs). This ability to modify the physical and chemical properties and functions of proteins render PTMs vital. To date, over 200 different protein modifications have been reported, owing to advanced detection technologies. Some of these modifications include phosphorylation, glycosylation, methylation, acetylation, and ubiquitination. Here, we discuss about the existing as well as some novel post-translational protein modifications, with their implications in aberrant states, which will help us better understand the modified sites in different proteins and the effect of PTMs on protein functions in core biological processes and progression in cancer.

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Section: The H33 Variant In Brain Development and Maturation As Well ...mentioning

confidence: 99%

“…It is also worth noting that, recently, a new kind of histone PTM was described: modification by monoamine neurotransmitters, such as dopamine and serotonin [ 85 , 86 , 87 , 88 ]. Some of these modifications seem to have H3 histones as specific targets [ 87 , 88 ]. For example, it was reported that serotonylation involves glutamine 5 of H3 histones and that the presence of this modified H3Q5 can, in turn, stabilize H3K4 methylation [ 89 ].…”

Section: The H33 Variant In Brain Development and Maturation As Well ...mentioning

confidence: 99%

Involvement of the H3.3 Histone Variant in the Epigenetic Regulation of Gene Expression in the Nervous System, in Both Physiological and Pathological Conditions

Schiera

Schirò

Liegro

2023

IJMS

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All the cells of an organism contain the same genome. However, each cell expresses only a minor fraction of its potential and, in particular, the genes encoding the proteins necessary for basal metabolism and the proteins responsible for its specific phenotype. The ability to use only the right and necessary genes involved in specific functions depends on the structural organization of the nuclear chromatin, which in turn depends on the epigenetic history of each cell, which is stored in the form of a collection of DNA and protein modifications. Among these modifications, DNA methylation and many kinds of post-translational modifications of histones play a key role in organizing the complex indexing of usable genes. In addition, non-canonical histone proteins (also known as histone variants), the synthesis of which is not directly linked with DNA replication, are used to mark specific regions of the genome. Here, we will discuss the role of the H3.3 histone variant, with particular attention to its loading into chromatin in the mammalian nervous system, both in physiological and pathological conditions. Indeed, chromatin modifications that mark cell memory seem to be of special importance for the cells involved in the complex processes of learning and memory.

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Post-translational modifications of histone proteins by monoamine neurotransmitters

Cited by 10 publications

References 40 publications

Histone H3 serotonylation dynamics in dorsal raphe nucleus contribute to stress- and antidepressant-mediated gene expression and behavior

Histone H3 serotonylation dynamics in dorsal raphe nucleus contribute to stress- and antidepressant-mediated gene expression and behavior

Post-translational modifications and their implications in cancer

Involvement of the H3.3 Histone Variant in the Epigenetic Regulation of Gene Expression in the Nervous System, in Both Physiological and Pathological Conditions

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