NGG1 (also called ADA3) encodes a component of three chromatin modifying histone acetyltransferase (HAT) complexes: SAGA, SLIK, and ADA (6, 7, 5; reviewed in 8). These complexes function in positive and negative transcriptional regulation of numerous RNA polymerase II-transcribed genes; in addition, SLIK plays a role in the retrograde response (5, 9; reviewed in 10). The three complexes each contain the histone acetyltransferase catalytic subunit Gcn5p, which interacts directly with Ada2p and preferentially modifies histones H3 and H2B (11; reviewed in 10). In vitro, Gcn5p acetylates N-terminal lysines on free histones, but acetylation of nucleosomal histone substrates also requires Ada2p and Ngg1p, which are found in a complex with Gcn5p (12). Ada2p has been shown to increase the HAT activity of Gcn5p, while Ngg1p plays a role in expanding the range of lysines that undergo acetylation (12).

Null mutations in NGG1 confer slow growth in minimal medium, no growth on any medium at 37 deg C, and resistance to the toxic effect of the chimeric transcriptional activator GAL4-VP16 (13). These null mutant phenotypes are complemented by the simultaneous expression of separate clones containing the NGG1 amino terminal half and carboxy terminal half, suggesting that Ngg1p has two domains and their covalent attachment is not required for function (6). The carboxy terminal domain interacts with Ada2p but not with Gcn5p in formation of the Ada2p-Ngg1p-Gcn5p complex (6). The amino terminal domain has been shown to interact with the transcriptional activation domains of Pdr1p and Prd3p (14), and is involved in transcriptional repression of the GAL genes by glucose (15).

Ngg1p is evolutionarily conserved among eukaryotes and orthologs have been described in several organisms, including Drosophila (16), Arabidopsis (17), and humans (18, 19). Human ADA3 interacts with p53 and is required for DNA damage-induced acetylation and consequent stabilization of p53 (20).

Last updated: 2010-03-26