Structural insights into the -- stacking mechanism and DNA-binding activity of the YEATS domain. Academic Article uri icon


  • The YEATS domain has been identified as a reader of histone acylation and more recently emerged as a promising anti-cancer therapeutic target. Here, we detail the structural mechanisms for -- stacking involving the YEATS domains of yeast Taf14 and human AF9 and acylated histone H3 peptides and explore DNA-binding activities of these domains. Taf14-YEATS selects for crotonyllysine, forming stacking with both the crotonyl amide and the alkene moiety, whereas AF9-YEATS exhibits comparable affinities to saturated and unsaturated acyllysines, engaging them through stacking with the acyl amide. Importantly, AF9-YEATS is capable of binding to DNA, whereas Taf14-YEATS is not. Using a structure-guided approach, we engineered a mutant of Taf14-YEATS that engages crotonyllysine through the aromatic-aliphatic-aromatic stacking and shows high selectivity for the crotonyl H3K9 modification. Our findings shed light on the molecular principles underlying recognition of acyllysine marks and reveal a previously unidentified DNA-binding activity of AF9-YEATS.

published proceedings

  • Nat Commun

altmetric score

  • 9.85

author list (cited authors)

  • Klein, B. J., Vann, K. R., Andrews, F. H., Wang, W. W., Zhang, J., Zhang, Y. i., ... Kutateladze, T. G.

citation count

  • 31

complete list of authors

  • Klein, Brianna J||Vann, Kendra R||Andrews, Forest H||Wang, Wesley W||Zhang, Jibo||Zhang, Yi||Beloglazkina, Anastasia A||Mi, Wenyi||Li, Yuanyuan||Li, Haitao||Shi, Xiaobing||Kutateladze, Andrei G||Strahl, Brian D||Liu, Wenshe R||Kutateladze, Tatiana G

publication date

  • November 2018