Zhang Nan, Wu Jinghua, Hossain Farzana, Peng Haidong, Li Huapeng, Gibson Connor, Chen Min, Zhang Huan, Gao Shuaixin, Zheng Xinru, Wang Yongdong, Zhu Jiangjiang, Wang Jing J, Maze Ian, Zheng Qingfei
Department of Radiation Oncology, College of Medicine, The Ohio State University, Columbus, Ohio 43210, United States.
Center for Cancer Metabolism, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, United States.
J Am Chem Soc. 2024 Jun 7. doi: 10.1021/jacs.4c04249.
Histone monoaminylation (., 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 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 and 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.
组蛋白单胺化（即5-羟色胺化和多巴胺化）是一种新出现的表观遗传标记类型，发生在H3 N端尾部的第五个谷氨酰胺（Q5）残基上，在基因转录中发挥重要作用。目前对组蛋白单胺化的分析主要基于位点特异性抗体和质谱，前者缺乏高分辨率，后者则耗时较长。在本研究中，我们报告了用于生物正交标记和富集组蛋白5-羟色胺化和多巴胺化的化学探针的开发。这些探针已成功应用于生化分析、细胞和组织样本的单胺化分析。探针富集单胺化组蛋白进一步证实了H3Q5单胺化与H3K4甲基化之间的相互作用。最后，结合基于所开发探针的[此处原文缺失相关内容]和[此处原文缺失相关内容]分析，我们发现组蛋白5-羟色胺化和多巴胺化在过表达转谷氨酰胺酶2（TGM2）的肿瘤组织中高度富集，并调节细胞染色质的三维结构。
