Role of histone acetylation in the assembly and modulation of chromatin structures

Abstract

The acetylation of the core histone N-terminal "tail" domains is now recognized as a highly conserved mechanism for regulating chromatin functional states. The following article examines possible roles of acetylation in two critically important cellular processes: replication-coupled nucleosome assembly, and reversible transitions in chromatin higher order structure. After a description of the acetylation of newly synthesized histones, and of the likely acetyltransferases involved, an overview of histone octamer assembly is presented. Our current understanding of the factors thought to assemble chromatin in vivo is then described. Genetic and biochemical investigations of the function the histone tails, and their acetylation, in nucleosome assembly are detailed, followed by an analysis of the importance of histone deacetylation in the maturation of newly replicated chromatin. In the final section the involvement of the histone tail domains in chromatin higher order structures is addressed, along with the role of histone acetylation in chromatin folding. Suggestions for future research are offered in the concluding remarks.

Figure 1

Overview of chromatin replication and assembly. Parental histone octamers segregate in groups to both sides of the replication fork, where their association with histone H1 is quickly reestablished. In the gaps produced by dispersive segregation, de novo nucleosome assembly proceeds in a stepwise fashion. First newly synthesized H3/H4 tetramers, acetylated in specific deposition-related patterns, are deposited onto the nascent DNA. Next, preexisting H2A/H2B dimers (generated through histone exchange in nonreplicating chromatin) associate with the H3/H4 tetramers. Lastly, histone H1 is deposited, and new H3 and H4 are deacetylated. Please see text for details and references.

Figure 2

General scheme describing the solution-state behavior of nucleosomal arrays. The number of asterisks (*) represents the degree to which the indicated functions of the N-termini can be replaced by high Mg²⁺ concentrations. See text for details.

Figure 3

Steps involved in the activation of eukaryotic genes. The steps that are most likely involve acetylation-dependent disruption of nucleosomal array condensation are shaded. See text for details.