Disease relevance of HAT1

• The HAT1 protein expressed in Escherichia coli gave histone acetyltransferase activity in vitro, demonstrating that HAT1 is the structural gene for the enzyme [1].

High impact information on HAT1

• Structure of the histone acetyltransferase Hat1: a paradigm for the GCN5-related N-acetyltransferase superfamily [2].
• A model for histone H4 binding by Hat1 is discussed in terms of possible sources of specific lysine recognition by the enzyme [2].
• 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 [2].
• The activity contains two proteins, Hat1p and Hat2p [3].
• In vivo, the nuclear Hat1p/Hat2p/Hif1p complex is bound to acetylated histone H4, as well as histone H3 [4].

Biological context of HAT1

• However, the role for these gene products in chromatin function has been unclear, as deletions of the HAT1 and/or HAT2 gene displayed no obvious phenotype [5].
• The catalytic subunits of both cytoplasmic and nuclear enzymes have identical molecular masses (42 kDa), the same as that of HAT1 [6].
• Epistasis analysis indicates that the histone H3 and HAT1 mutants may influence DNA double-strand break repair through Asf1p-dependent chromatin assembly [7].
• As many gene products, including other factors involved in chromatin assembly, have been found to participate in both telomeric silencing and DNA damage repair, we tested whether mutations in HAT1 and the histone H3 tail were also sensitive to DNA-damaging agents [7].
• Thus, in contrast to other histone acetyltransferases, Hat1p activity was required for transcriptional repression rather than gene activation [5].

Associations of HAT1 with chemical compounds

• Indeed, mutations both in specific lysine residues in the histone H3 tail and in HAT1 resulted in sensitivity to methyl methanesulfonate [7].
• Finally, we have demonstrated that deletion of the hat1 gene from the fission yeast Schizosaccharomyces pombe causes increased sensitivity to the DNA-damaging agent methyl methanesulfonate in the absence of any additional mutations [8].

Physical interactions of HAT1

• The nuclear Hat1p/Hat2p complex: a molecular link between type B histone acetyltransferases and chromatin assembly [4].

Other interactions of HAT1

• HAT-B is a yeast histone acetyltransferase composed of Hat1, Hat2 and Hif1 proteins [9].
• 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 [6].

Analytical, diagnostic and therapeutic context of HAT1

• In a localization analysis by immunofluorescence microscopy on yeast strains expressing tagged versions of Hat1, Hat2, and Hif1, we have found that all three HAT-B proteins are mainly localized in the nucleus [10].

References