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Histone serotonylation is a permissive modification that enhances TFIID binding to H3K4me3

Item Type:Article
Title:Histone serotonylation is a permissive modification that enhances TFIID binding to H3K4me3
Creators Name:Farrelly, L.A. and Thompson, R.E. and Zhao, S. and Lepack, A.E. and Lyu, Y. and Bhanu, N.V. and Zhang, B. and Loh, Y.H.E. and Ramakrishnan, A. and Vadodaria, K.C. and Heard, K.J. and Erikson, G. and Nakadai, T. and Bastle, R.M. and Lukasak, B.J. and Zebroski, H. and Alenina, N. and Bader, M. and Berton, O. and Roeder, R.G. and Molina, H. and Gage, F.H. and Shen, L. and Garcia, B.A. and Li, H. and Muir, T.W. and Maze, I.
Abstract: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.
Keywords:Cell Differentiation, Cell Line, Gene Expression Regulation, Glutamine, GTP-Binding Proteins, Histones, Inbred C57BL Mice, Lysine, Methylation, Post-Translational Protein Processing, Protein Binding, Serotonergic Neurons, Serotonin, Transcription Factor TFIID, Transglutaminases, Animals, Mice
Source:Nature
ISSN:0028-0836
Publisher:Nature Publishing Group (U.K.)
Volume:567
Number:7749
Page Range:535-539
Date:28 March 2019
Official Publication:https://doi.org/10.1038/s41586-019-1024-7
PubMed:View item in PubMed

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