HGNC Approved Gene Symbol: HAT1
Cytogenetic location: 2q31.1 Genomic coordinates (GRCh38) : 2:171,922,461-171,983,686 (from NCBI)
The reversible acetylation of specific lysine residues within the N-terminal tails of the core histones is correlated with gene activity. Histone acetylation, particularly of histone H4, has also been proposed to play an important role in replication-dependent nucleosome assembly (summary by Dutnall et al., 1998). The S. cerevisiae Hat1 gene was the first histone acetyltransferase gene to be identified, and its gene product was found to be tightly associated with an accessory protein.
By searching an expressed sequence tag database with the S. cerevisiae Hat1 sequence, Verreault et al. (1998) isolated a cDNA (GenBank AF030424) encoding HAT1, the human ortholog of yeast Hat1. The sequences of the human and yeast HAT1 proteins are 29% identical and 55% similar. The deduced 419-amino acid human HAT1 contains D, A, and B motifs, which are present in many N-acetyltransferases, including those that acetylate substrates other than histones. HAT1 also contains a putative bipartite nuclear localization signal; however, deletion of this signal had no effect on the intranuclear localization of HAT1. The authors purified the HAT1 holoenzyme from human 293 cells and found that it consists of 2 subunits: the catalytic 46-kD HAT1 and the accessory p46 (RBBP7; 300825). The p46 subunit stimulated the activity of HAT1 and bound to core histones. The HAT1 holoenzyme acetylated newly synthesized but not nucleosomal histone H4 at lys5 and lys12, and, to a lesser extent, histone H2A at lys5. Verreault et al. (1998) showed that the HAT1 and p46 polypeptides are located in the nucleus of S-phase cells.
In their GenBank submission, Verreault et al. (1998) indicated that the HAT1 gene maps to 2q31.2-q33.1.
Crystal Structure
Dutnall et al. (1998) determined the crystal structure of the yeast Hat1-acetyl CoA (AcCoA) complex at 2.3-angstrom resolution. Hat1 has an elongated, curved structure, and the AcCoA molecule is bound in a cleft on the concave surface of the protein, marking the active site of the enzyme. A channel of variable width and depth that runs across the protein is probably the binding site for the histone substrate. Dutnall et al. (1998) discussed a model for histone H4 binding by Hat1 in terms of possible sources of specific lysine recognition by the enzyme.
Dutnall, R. N., Tafrov, S. T., Sternglanz, R., Ramakrishnan, V. Structure of the histone acetyltransferase Hat1: a paradigm for the GCN5-related N-acetyltransferase superfamily. Cell 94: 427-438, 1998. [PubMed: 9727486] [Full Text: https://doi.org/10.1016/s0092-8674(00)81584-6]
Verreault, A., Kaufman, P. D., Kobayashi, R., Stillman, B. Nucleosomal DNA regulates the core-histone-binding subunit of the human Hat1 acetyltransferase. Curr. Biol. 8: 96-108, 1998. [PubMed: 9427644] [Full Text: https://doi.org/10.1016/s0960-9822(98)70040-5]