The histone H4 acetyltransferase MOF uses a C2HC zinc finger for substraterecognition

Site-specific acetylation of histone H4 by MOF is central to establishing t he hyperactive male X chromosome in Drosophila. MOF belongs to the MYST fam ily of histone acetyltransferases (HATs) characterized by an unusual C2HC-t ype zinc finger close to their HAT domains. The function of these rare zinc fingers is unknown. We found that this domain is essential for HAT activit y, in addition to the established catalytic domain. MOF uses its zinc finge r to contact the globular part of the nucleosome as well as the histone H4 N-terminal tail substrate. Point mutations that leave the zinc-finger struc ture intact nevertheless abolish its interaction with the nucleosome. Our d ata document a novel role of the C2HC-type finger in nucleosome binding and HAT activity.