Bioorthogonal Labeling and Enrichment of Histone Monoaminylation Reveal Its Accumulation and Regulatory Function in Cancer Cell Chromatin

Nan Zhang, Jinghua Wu, Farzana Hossain, Haidong Peng, Huapeng Li, Connor Gibson, Min Chen, Huan Zhang, Shuaixin Gao, Xinru Zheng, Yongdong Wang, Jiangjiang Zhu, Jing J. Wang, Ian Maze, Qingfei Zheng

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Histone monoaminylation (i.e., serotonylation and dopaminylation) is an emerging category of epigenetic mark occurring on the fifth glutamine (Q5) residue of H3 N-terminal tail, which plays significant roles in gene transcription. Current analysis of histone monoaminylation is mainly based on site-specific antibodies and mass spectrometry, which either lacks high resolution or is time-consuming. In this study, we report the development of chemical probes for bioorthogonal labeling and enrichment of histone serotonylation and dopaminylation. These probes were successfully applied for the monoaminylation analysis of in vitro biochemical assays, cells, and tissue samples. The enrichment of monoaminylated histones by the probes further confirmed the crosstalk between H3Q5 monoaminylation and H3K4 methylation. Finally, combining the ex vivo and in vitro analyses based on the developed probes, we have shown that both histone serotonylation and dopaminylation are highly enriched in tumor tissues that overexpress transglutaminase 2 (TGM2) and regulate the three-dimensional architecture of cellular chromatin.

Original languageEnglish
Pages (from-to)16714-16720
Number of pages7
JournalJournal of the American Chemical Society
Volume146
Issue number24
DOIs
StatePublished - 19 Jun 2024

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