Histone acetyltransferase 1: more than just an enzyme?

Abstract

Histone acetyltransferase 1 (HAT1) is an enzyme that is likely to be responsible for the acetylation that occurs on lysines 5 and 12 of the NH2-terminal tail of newly synthesized histone H4. Initial studies suggested that, despite its evolutionary conservation, this modification of new histone H4 played only a minor role in chromatin assembly. However, a number of recent studies have brought into focus the important role of both this modification and HAT1 in histone dynamics. Surprisingly, the function of HAT1 in chromatin assembly may extend beyond just its catalytic activity to include its role as a major histone binding protein. These results are incorporated into a model for the function of HAT1 in histone deposition and chromatin assembly. This article is part of a Special issue entitled: Histone chaperones and Chromatin assembly.

Figure 1. Model for the function of Hat1 in chromatin assembly

The Hat1 core complex (Hat1 and Hat2/Rbap46) initially interacts with newly synthesized histones H3 and H4 and modifies the H4 by acetylating lysines 5 and 12. This complex may then interact with Asf1 and facilitate the association of the histones with their cognate nuclear import factor. The Hat1 core complex also transits to the nucleus where it is predominantly localized. Whether the Hat1 core complex can be co-transported with histone H3 and H4 is not known. Once inside the nucleus, the Hat1 core complex makes a number of interactions. The Hat1 core complex can interact with the origin recognition complex (ORC) and localize to origins of replication. The bulk of the Hat1 core complex forms the NuB4 complex with the addition of an N1 family histone chaperone (Hif1p or NASP). The NuB4 complex also appears to interact with Asf1. This interaction may be part of the pathway for deposition of newly synthesized histones or may be necessary for the modification of recycled histones. The NuB4 complex also functions independently of Asf1 and may be a component of a separate chromatin assembly pathway that functions in DNA repair-linked chromatin reassembly and may act in other chromatin assembly pathways, as well.