The N-terminal region of CHD4 is essential for activity and contains a HMG-box-like-domain that can bind poly(ADP-ribose).
Silva AP, Ryan DP, Galanty Y, Low JK, Vandevenne M, Jackson SP, Mackay JP. Journal of Biological Chemistry 291, 924-938.
Chromodomain Helicase DNA-binding protein 4 (CHD4) is a chromatin-remodeling enzyme that has been reported to regulate DNA damage responses through its N-terminal region in a poly(ADP-ribose) polymerase dependent manner. We have identified and determined the structure of a stable domain (CHD4-N) in this Nterminal region. The fold consists of a four α-helix bundle with structural similarity to the High Mobility Group (HMG) box, a domain that is well known as a DNA-binding module. We show that the CHD4-N domain binds with higher affinity to poly(ADP-ribose) than to DNA. We also show that the N-terminal region of CHD4, although not CHD4-N alone, is essential for full nucleosome remodeling activity and is important for localizing CHD4 to sites of DNA damage. Overall, these data build on our understanding of how CHD4/NuRD acts to regulate gene expression and participates in the DNA-damage response.