HOMERevealing the molecular mechanism of a molecular motor controlling DNA high-order structure
Prof. Song’s group at the Department of Biological Sciences of KIB investigated the molecular mechanism of the CHD7 molecular motor, which utilizes ATP as an energy source to reorganize the DNA- high- order structure.
Chromodomain-Helicase DNA binding protein 7 (CHD7) is an ATP- dependent chromatin remodeler is involved in maintaining the open chromatin structure. Mutations of the CHD7 gene cause multiple developmental disorders, notably CHARGE syndrome. However, there is not much known about the molecular mechanism by which CHD7 remodels nucleosomes. Here, we conducted biochemical and biophysical analyses of the CHD7 chromatin remodeler and found that the N-terminal of the chromodomain (N-CRD) interacts with the nucleosome and contains a highly conserved arginine stretch, which is reminiscent of an arginine anchor.
Importantly, this region is required for the efficient ATPase stimulation and nucleosome remodeling activity of CHD7. Furthermore, a smFRET analysis shows mutations in the N-CRD cause defects in the remodeling activity. Collectively, our results uncover the functional importance of a previously unidentified N-terminal region in CHD7 and suggest that multiple domains in the chromatin remodelers are involved in regulating their activities.
Prof. Ji-Joon Song
2021 KI Newsletter