HAT1 and HAT2 Proteins Are Components of a Yeast Nuclear Histone Acetyltransferase Enzyme Specific for Free Histone H4

Abstract

We have analyzed the histone acetyltransferase enzymes obtained from a series of yeast hat1, hat2, and gcn5 single mutants and hat1,hat2 and hat1,gcn5 double mutants. Extracts prepared from both hat1 and hat2 mutant strains specifically lack the following two histone acetyltransferase activities: the well known cytoplasmic type B enzyme and a free histone H4-specific histone acetyltransferase located in the nucleus. The catalytic subunits of both cytoplasmic and nuclear enzymes have identical molecular masses (42 kDa), the same as that of HAT1. However, the cytoplasmic complex has a molecular mass (150 kDa) greater than that of the nuclear complex (110 kDa). The possible functions of HAT1 and HAT2 in the yeast nucleus are discussed. In addition, we have detected a yeast histone acetyltransferase not previously described, designated HAT-A4. This enzyme is located in the nucleus and is able to acetylate free and nucleosome-bound histones H3 and H4. Finally, we show that the hat1,gcn5 double mutant is viable and does not exhibit a new phenotype, thus suggesting the existence of several histone acetyltransferases with overlapping functions.

Gcn5p, a Transcription-related Histone Acetyltransferase, Acetylates Nucleosomes and Folded Nucleosomal Arrays in the Absence of Other Protein Subunits

“…Hat1p is the catalytic subunit of both the major cytoplasmic HAT-B complex and the nuclear HAT-A3 complex (8). Consistent with their roles in nucleosome assembly, recombinant Hat1p, the HAT-B complex, and the HAT A-3 complex all acetylate free histone H4 in vitro but do not acetylate H4 after its incorporation into nucleosomes (5,6,8,9).…”

“…Consistent with their roles in nucleosome assembly, recombinant Hat1p, the HAT-B complex, and the HAT A-3 complex all acetylate free histone H4 in vitro but do not acetylate H4 after its incorporation into nucleosomes (5,6,8,9). However, seemingly at odds with its role as a HAT-A enzyme, Gcn5p has been reported to acetylate free histones H3 and H4 but not nucleosomal H3 or H4 (10 -13).…”

“…The HAT-A enzymes reside in the nucleus and acetylate the core histone N termini following their assembly into nucleosomes and chromatin. HAT-B type enzymes are primarily cytoplasmic and acetylate only free histones prior to nucleosome assembly (6), although Hat1p has recently been localized in the nucleus as well (8).…”

Hat1: the emerging cellular roles of a type B histone acetyltransferase

“…Deletion of the gene encoding HAT1 not only eliminates the H4-specific histone acetyltransferase present in cytoplasmic extracts, but also causes the loss of an activity present in nuclear extracts as well (Parthun et al, 1996;Ruiz-Garcia et al, 1998). Also, distinct Hat1/Hat2-containing complexes can be purified from both cytoplasmic and nuclear extracts (Ai and Parthun, 2004;Poveda et al, 2004).…”

Three Yeast Proteins Related to the Human Candidate Tumor Suppressor p33ING1 Are Associated with Histone Acetyltransferase Activities

“…In Saccharomyces cerevisiae, proteins that possess HAT activity include Hat1 (36), Gcn5 (11), and Esa1 (68). Hat1 is localized in both the cytosol and nucleus and acetylates primarily newly synthesized histone H4 prior to its assembly into nucleosomes (36,55,60,78). Gcn5 is a nuclear HAT that preferentially acetylates H3, and to a lesser extent it acetylates H2B and H4 (25).…”