The interaction of DNA with multi-Cys2His2 zinc finger proteins

The multi-Cys2His2 (mC2H2) zinc finger protein, like CTCF, plays a central role in the three-dimensional organization of chromatin and gene regulation. The interaction between DNA and mC2H2 zinc finger proteins becomes crucial to better understand how CTCF dynamically shapes the chromatin structure. Here, we study a coarse-grained model of the mC2H2 zinc finger proteins in complexes with DNA, and in particular, we study how a mC2H2 zinc finger protein binds to and searches for its target DNA loci. On the basis of coarse-grained molecular dynamics simulations, we present several interesting kinetic conformational properties of the proteins, such as the rotation-coupled sliding, the asymmetrical roles of different zinc fingers and the partial binding partial dangling mode. In addition, two kinds of studied mC2H2 zinc finger proteins, of CG-rich and AT-rich binding motif each, were able to recognize their target sites and slide away from their non-target sites, which shows a proper sequence specificity in our model and the derived force field for mC2H2-DNA interaction. A further application to CTCF shows that the protein binds to a specific DNA duplex only with its central zinc fingers. The zinc finger domains of CTCF asymmetrically bend the DNA, but do not form a DNA loop alone in our simulations.