The Histone Acetyltransferase NCOAT Contains a Zinc Finger-like Motif Involved in Substrate Recognition

Abstract

Nuclear cytoplasmic O-GlcNAcase and acetyltransferase (NCOAT) is a bifunctional enzyme with both glycoside hydrolase and alkyltransferase activity. Its O-GlcNAcase active site lies in the N terminus of the enzyme and its histone acetyltransferase (HAT) domain lies in the C terminus. Whereas the HAT domain of the enzyme is catalytically and structurally similar to other acetyltransferases across subfamilies, NCOAT has a motif resembling a zinc finger-like domain unique to the MYST family of HATs. Among the MYST family, this zinc finger, or zinc finger-like domain, is responsible for making contacts with the histone tails within nucleosomes for the HAT to catalyze its respective reaction. Here, we show that NCOAT has the ability to directly associate with both an acetylated and unacetylated histone H4 tail in vitro, and a potential zinc finger-like motif found in NCOAT is implicated in this nucleosomal contact, and is necessary for fully efficient enzymatic activity. Subsequent to the catalysis of acetyltransfer to lysine 8 of histone H4 for the enzyme, however, the substrate is released and NCOAT can no longer bind H4 in our assays. Furthermore, this finger domain by itself is sufficient to bind histone H4.

Structural Basis of Eco1-Mediated Cohesin Acetylation

“…Unlike other GNAT family members, Eco1 contains a zinc-finger (ZnF) domain that is similar to those found in the Moz/Ybfs/Sas2/Tip60 (MYST) family of histone acetyltransferases (HATs). The ZnF is responsible for HATs recognizing nucleosome in histone tail acetylation181920, while in Eco1, the ZnF enhances its acetyltransferase activity during sister chromatid cohesion21. Its S-phase localization to the replication fork is thought to be via a direct interaction with PCNA222324.…”

Epigenetic Switching by the Metabolism-sensing Factors in the Generation of Orexin Neurons from Mouse Embryonic Stem Cells

“…Importantly, Mgea5 has both Oga and HAT activities (22,45). The zinc finger-like motif of Mgea5 is responsible for the recognition of the acetyl substrate (55). Mgea5 showed HAT activity and the capability to modify all core histones in vitro, which include H3K14 and H4K8.…”

Caenorhabditis elegans ortholog of a diabetes susceptibility locus: oga-1 ( O -GlcNAcase) knockout impacts O -GlcNAc cycling, metabolism, and dauer

“…The histone acetyltransferase (HAT) domain contains a zinc finger-like motif unique to the MYST family of HATs and interacts with histone tails (16). The gene encoding OGA has not been knocked out in mice, and no null alleles of OGA have been described.…”