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Histone Glutamine Modification by Neurotransmitters: Paradigm Shift in the Epigenetics of Neuronal Gene Activation and Dopaminergic VTA Reward Pathway

Q-Epigenetics and Neurotransmitters


  • Samir Kumar Patra Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha



Normal brain function means fine-tuned neuronal circuitry with optimum neurotransmitter signaling. The classical views and experimental demonstrations established neurotransmitters release-uptake through synaptic vesicles. Current research highlighted that neurotransmitters not merely influence electrical impulses; however, contribute to gene expression, now we know, by posttranslational modifications of chromatinised histones. Epigenetic modifications of chromatin, like DNA methylation, histone methylation, acetylation, ubiquitilation etc., influence gene expression during neuronal development, differentiation and functions. Protein glutamine (Q) modification by tissue transglutaminase (TGM2) controls a wide array of metabolic and signaling activities, including neuronal functions. Dopamine neurons are central element in the brain reward system that controls the learning of numerous behaviours. The ventral tegmental area (VTA) consists of dopamine, GABA, or glutamate neurons. The VTA and adjacent substantia nigra are the two major dopaminergic areas in the brain. In view of this, and to focus insight into the neuronal functions caused by TGM2 mediated histone modifications at the Q residues, either serotonylation (for example, H3K4me3Q5 to H3K4me3Q5ser) in the context of cellular differentiation and signaling, or dopaminylation (for example, H3Q5 to H3Q5dop) in the dopaminergic VTA reward pathway and the precise role of cocaine withdrawal in this scenario are summarized and discussed in this contribution.


Neurotransmission, Epigenetics, Glutamine modifications, Tissue transglutaminase 2, Ventral tegmental area, Reward system


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