Chemical synthesis of histone H2A with methylation at Gln104

Histone H2A methylation at Glnl04 （H2AQ104Me） is a new type of histone post-translational modification （PTM） discovered recently. This modification has been found to have significant influence on gene transcription. However, the structural and fimctional consequence of glutamine methylation on nucleosome remains to be further elucidated. Obtaining of histones with site-specific methylation at glutamine residues might facilitate the studies towards a better understanding of this new PTM. In the present work, total chemical synthesis of H2AQ 104Me was carried out through use of the hydrazide-based native chemical ligation. Synthetic histone H2AQ104Me could be successfully incorporated into nucleosomes in vitro and showed a negative influence on the nucleosome stability.