We report the cloning of a transcription-associated histone acetyltransferase type A(HAT A). This Tetrahymena enzyme is strikingly homologous to the yeast protein Gcn5, a putative transcriptional adaptor, and we demonstrate that recombinant Gcn5p possesses HAT activity. Both the ciliate enzyme and Gcn5p contain potential active site residues found in other acetyltransferases and a highly conserved bromodomain. The presence of this domain in nuclear A-type HATs, but not in cytoplasmic B-type HATs, suggests a mechanism whereby HAT A is directed to chromatin to facilitate transcriptional activation. These findings shed light on the biochemical function of the evolutionarily conserved Gcn5p-Ada complex, directly linking histone acetylation to gene activation, and indicate that histone acetylation is a targeted phenomenon.

Myogenin is a muscle-specific transcription factor that can induce myogenesis in a variety of cell types in tissue culture. To test myogenin's role in vivo, mice homozygous for a targeted mutation in the myogenin gene were generated. These mice survive fetal development but die immediately after birth and show a severe reduction of all skeletal muscle. Myogenin-mutant mice differ from mice carrying mutations in genes for the related myogenic factors Myf5 and MyoD, which have no muscle defects. Myogenin is therefore essential for the development of functional skeletal muscle.

The yeast transcriptional adaptor, Gcn5p, is a catalytic subunit of a nuclear (type A) histone acetyltransferase linking histone acetylation to gene activation. Here we report that Gcn5p acetylates histones H3 and H4 non-randomly at specific lysines in the amino-terminal domains. Lysine 14 of H3 and lysines 8 and 16 of H4 are highly preferred acetylation sites for Gcn5p. We also demonstrate that lysine 9 is the preferred position of acetylation in newly synthesized yeast H3 in vivo. This finding, along with the fact that lysines 5 and 12 in H4 are predominant acetylation sites during chromatin assembly of many organisms, indicates that Gcn5p acetylates a distinct set of lysines that do not overlap with those sites characteristically used by type B histone acetyltransferases for histone deposition and chromatin assembly.

The sequence for the open reading frame of the mouse myogenin eDNA contains two errors, which were detected while sequencing the corresponding genomic clone. Codon 124 encodes Ser instead of His, and an additional dC is present at codon 155. This results in a frameshift in the carboxy-terminal portion of the protein. These errors have been confirmed by resequencing the cDNAs on both strands. The corrected sequence is shown below and has been submitted to GenBank.

Repression of yeast a cell-specific genes by the global repressor Ssn6lTupl has been linked to a specific organization of chromatin. We report here that Tupl directly interacts with the amino-terminal tails of histones H3 and H4, providing a molecular basis for this connection. This interaction appears to be required for Tupl function because amino-terminal mutations in H3 and H4 that weaken interactions with Tupl cause derepression of both a cell-specific and DNA damage-inducible genes. Moreover, the Tupl histone-binding domain coincides with the previously defined Tupl repression domain. Tupllhistone interactions are negatively influenced by high levels of histone acetylation, suggesting a mechanism whereby the organization of chromatin may be modulated in response to changing environmental signals.