TY - JOUR
T1 - Bioorthogonal Labeling and Enrichment of Histone Monoaminylation Reveal Its Accumulation and Regulatory Function in Cancer Cell Chromatin
AU - Zhang, Nan
AU - Wu, Jinghua
AU - Hossain, Farzana
AU - Peng, Haidong
AU - Li, Huapeng
AU - Gibson, Connor
AU - Chen, Min
AU - Zhang, Huan
AU - Gao, Shuaixin
AU - Zheng, Xinru
AU - Wang, Yongdong
AU - Zhu, Jiangjiang
AU - Wang, Jing J.
AU - Maze, Ian
AU - Zheng, Qingfei
N1 - Publisher Copyright:
© 2024 American Chemical Society.
PY - 2024/6/19
Y1 - 2024/6/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85195283916&partnerID=8YFLogxK
U2 - 10.1021/jacs.4c04249
DO - 10.1021/jacs.4c04249
M3 - Article
C2 - 38848464
AN - SCOPUS:85195283916
SN - 0002-7863
VL - 146
SP - 16714
EP - 16720
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 24
ER -