2026 Volume 101 Article ID: 25-00096
VANDAL family DNA transposons are prevalent in Arabidopsis and related plants. A notable feature of VANDALs is that they can overcome epigenetic silencing from the host, using a VANC protein encoded in each VANDAL member: VANC21 protein encoded in VANDAL21 specifically accumulates on its target DNA motifs that are concentrated in the non-coding regions of this TE and induces loss of DNA methylation, transcriptional derepression, and mobilization of the element. In this study, to elucidate the mechanism of how VANC subtypes have diverged to bind specifically to their own target motifs in their cognate VANDAL subfamilies, we determined the crystal structure of VANC21 in complex with its target DNA at 2.0 Å resolution. The VANC structure adopts a globular novel fold with a Zn ion coordinated at the DNA-binding site. Interestingly, most DNA-interacting VANC residues are located in the loops but not in the conserved regions among VANC subtypes. This observation suggests that the high variability of DNA-interacting regions of VANC proteins brought about the co-evolution of VANCs and their target sequences. This rapid differentiation by co-evolution enabled VANDAL family TEs to proliferate while avoiding deleterious effects on host fitness. Therefore, our findings help to understand the adaptive evolutionary strategy for the survival of parasitic sequences.
