Structure and function of histone acetyltransferases

Abstract. Histone acetyltranferase (HAT) enzymes are the catalytic subunit of large multisubunit HAT complexes that acetylate the ε-amino group of specific lysine residues on histone tails to promote transcriptional activation. Recent structural and functional studies on the divergent HAT enzymes Gcn5/PCAF, Esa1 and Hat1 have provided new insights into the underlying mechanism of histone binding and acetylation by HAT proteins. The three HAT enzymes contain a structurally conserved core domain that plays a functionally conserved role in binding the coenzyme A cofactor and in harboring the putative general base for catalysis. Structurally variable N- and C-terminal domains appear to contain a related scaffold that mediates histone substrate binding. These data provide a framework for understanding the structure and function of other more divergent HAT proteins such as TAFII250 and CBP/p300, and provides a starting point for understanding how HAT proteins may cooperate with other factors within in vivo HAT complexes to promote transcriptional activation.

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