We discovered that CDCA7, a regulator of the chromatin remodeling factor HELLS, has hemimethylated DNA binding ability. The binding of CDCA7 to hemimethylation sites in nucleosomes was elucidated by cryo-EM. Although UHRF1 was previously reported as the only protein with the ability to bind hemimethylated DNA, UHRF1 was known to be unable to bind to hemimethylation sites in nucleosomes. Therefore, our results suggest that CDCA7 binds to hemimethylation sites in nucleosomes and recruits HELLS, creating a binding site for UHRF1 by moving the hemimethylation sites out of the nucleosome, where the downstream maintenance methylation mechanism is activated. The findings have led to the understanding of a novel molecular mechanism of DNA maintenance methylation in heterochromatin regions.
This work is collaboration with Professor Hironori Funabiki and Dr. Isabel E. Wassing, The Rockefeller University, and Associate Professor Atsuya Nishiyama, The University of Tokyo.