Dual mechanisms for the antagonistic crosstalk between H3 glycation and H3K4me3 [CUT&Tag]

Histones are particularly susceptible to glycation, resulting in substantial alterations to chromatin structure and the epigenetic landscape. However, the mechanism by which histone glycation alters epigenetic landscape and impacts specific transcriptional output in vivo has remained unclear due to the lack of high-resolution tools.

Here, we utilize adduct-, site-, and target-specific antibodies we developed against histone H3 glycation at arginine 17 (H3R17MG-H1), one of the most abundant histone glycation marks, to perform precise detection and enrichment of this mark. With these, we show that H3 glycation preferentially accumulates in euchromatin and directly crosstalks with a key active transcription-associated mark, H3K4me3, at transcription start sites.