Dual mechanisms for the antagonistic crosstalk between H3 glycation and H3K4me3

These include methylglyoxal (MGO), which can non-enzymatically modify macromolecules in a process known as glycation. Histones are particularly susceptible to glycation, resulting in substantial alterations to chromatin structure and the epigenetic landscape.

However, the mechanism by which this impacts specific transcriptional outputs has been difficult to interrogate due to the lack of high-resolution tools. Here, we utilize adduct-, site-, and target-specific antibodies we developed against glycated histone H3 arginine 17 (H3R17MG-H1), one of the most abundant histone glycation marks, to determine its chromatin localization. We show that H3R17MG-H1 preferentially accumulates in euchromatin and directly crosstalks with H3K4me3, a key positive mark of activity at transcription start sites.