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

Nature 2019 Mar; 567(7749):535-539. doi: 10.1038/s41586-019-1024-7. Epub 2019 Mar 13.

Lorna A Farrelly 1Robert E Thompson 2Shuai Zhao 3 4Ashley E Lepack 1Yang Lyu 1Natarajan V Bhanu 5Baichao Zhang 3 4Yong-Hwee E Loh 1Aarthi Ramakrishnan 1Krishna C Vadodaria 6Kelly J Heard 6Galina Erikson 6Tomoyoshi Nakadai 7Ryan M Bastle 1Bradley J Lukasak 2Henry Zebroski 3rd 8Natalia Alenina 9Michael Bader 9Olivier Berton 1Robert G Roeder 7Henrik Molina 8Fred H Gage 6Li Shen 1Benjamin A Garcia 5Haitao Li 3 4Tom W Muir 2Ian Maze 10 11

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Abstract

Chemical modifications of histones can mediate diverse DNA-templated processes, including gene transcription1-3. 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 TFIID4-6 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 signaling, in the mediation of permissive gene expression.

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About S. R. Zelenz 102 Articles
S.R. Zelenz has worked in education for 20 years. Working with students from all walks of life, cultures, races, and social diversity, Zelenz’s research in Educational Leadership led to finding a better way to approach learning for students with trauma histories. Many were juvenile offenders, gang members, diagnosed with varying behavioral disorders, or had family histories of violence, murder, or narcissistic parenting. This research could not be effectively accomplished without further understanding: how epigenetic trauma inheritance may be impacting these students; how brain development from trauma may be impacting their behavioral and emotional development; as well as deep understanding of psychology and its varying classifications for behavioral and personality disorders. The goal is to find solutions for changing the conversation and making a real difference for these students. She has also worked with nonprofits of varying focus areas for the last 25 years. Her undergraduate degree in Arts Administration and Music prepared her for managing nonprofits of any size as well as procuring funding so that they can achieve their goals. Pairing her nonprofit background with her education background, she has been able to make a difference for over 200 nonprofits worldwide, written curriculum for schools across the globe, and assisted many arts organizations through performance and management.