DNA G-quadruplexes (G4s) are key structural features in chromatin that are important to genome function. G4s have an apparent capacity to recruit a wide variety of proteins, including chromatin remodelers, yet the molecular basis and biophysical principles governing these interactions remain poorly understood. Here, we sought to build insights into the interactions of chromatin remodeler SMARCA4 with G4s using a biophysical approach. We found that SMARCA4 selectively recognizes the G4 structure over duplex and single-stranded DNA. SMARCA4 binds a wide range of G4s with different topologies and loop lengths with similar low nanomolar affinities. SMARCA4 was also observed to have a longer residency time on the G4 structure compared to that of other known protein-DNA interactions. We also found that the D1 (DExx-c) helicase domain of SMARCA4, which is important for tethering SMARCA4 to chromatinized DNA, was the predominant binding domain for G4 recognition. Our findings reveal new insights into how G4s interact with proteins, which may have important implications for understanding G4-mediated genome mechanisms.
Madden et al. (Fri,) studied this question.