Bioorthogonal labeling and enrichment of histone monoaminylation reveal its accumulation and regulatory function in cancer cell chromatin

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 ofin vitrobiochemical 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 theex vivoandin vitroanalyses 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.TOC <jats:fig id="ufig1" position="float" fig-type="figure" orientation="portrait"><jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="586010v3_ufig1" position="float" orientation="portrait" /></jats:fig>.

Medienart:

Preprint

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

bioRxiv.org - (2024) vom: 01. Apr. Zur Gesamtaufnahme - year:2024

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext [kostenfrei]

Themen:

570
Biology

doi:

10.1101/2024.03.20.586010

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

XBI043004385