Histone deacetylase

Abstract

Core histones can be modified by reversible, posttranslational acetylation of specific lysine residues within the N-terminal protein domains. The dynamic equilibrium of acetylation is maintained by two enzyme activities, histone acetyltransferase and histone deacetylase. Recent data on histone deacetylases and on anionic motifs in chromatin-or DNA-binding regulatory proteins (e.g. transcription factors, nuclear proto-oncogenes) are summarized and united into a hypothesis which attributes a key function to histone deacetylation for the binding of regulatory proteins to chromatin by a transient, specific local increase of the positive charge in the N-terminal domains of nucleosomal core histones. According to our model, the rapid deacetylation of distinct lysines in especially H2A and H2B would facilitate the association of anionic protein domains of regulatory proteins to specific nucleosomes. Therefore histone deacetylation (histone deacetylases) may represent a unique regulatory mechanism in the early steps of gene activation, in contrast to the more structural role of histone acetylation (histone acetyltransferases) for nucleosomal transitions during the actual transcription process.

Involvement of histone hyperacetylation in triggering DNA fragmentation of rat thymocytes undergoing apoptosis

“…The intact and fragmented DNAs in the Recently, it has been shown that acetylation, one of the postcells were assayed as described previously [12]. DNA fragmentation translational modifications of core histones [3], induces unwas expressed as a percentage of total DNA (intact plus fragmented folding of the chromatin fiber [4,5]. DNA).…”

Purification of histone deacetylase HD1‐A of germinating maize embryos

“…In most experimental systems investigated so far histone acetyltransferases and deacetylases exist as multiple enzyme forms; in pea, three histone deacetylases exist [26]. In maize we could distinguish four histone deacetylases [16,17,20,22,29]. The four histone deacetylases of maize are distinct with respect to their biochemical and kinetic properties [29], to modification by phosphorylation [20], pattern of enzyme activity during the cell cycle and differentiation [16][17][18], substrate specificity [16,20,29] and subnuclear localization [22].…”

“…The amino terminal histone tails can be acetylated at certain lysine residues, resulting in a decrease of the net positive charge on one hand, and in an alteration of their specific binding properties for regulatory proteins on the other hand. A change in the specific acetylation pattern of core histones has therefore been correlated with changes in the transcriptional activity of genes [11,[42][43][44]. Core histone N-termini and their acetylation also play a complex, but still poorly understood role in DNA replication [14,15,45].…”

“…The steady state of histone acetylation is maintained by two enzyme activities, histone acetyltransferase and histone deacetylase. These enzyme activities are present as multiple enzyme forms whose activities, properties, intracellular/intranuclear location and substrate specificities are regulated in a complex, cell cycle-related manner [16][17][18][19][20][21][22].…”

“…In maize four different histone deacetylases can be distinguished during embryo ger-*Corresponding author. Fax: (43) (512) 507 2866. mination [16,17,20,22,29]; these enzymes differ considerably from each other in terms of substrate specificity, intranuclear location, kinetic properties and posttranslational modification. In yeast a nuclear histone deacetylase could be isolated as a high molecular weight complex (> 350 kDa) at low ionic strength [27]; when the ionic strength was increased to 0.5 M NH4C1, the enzyme activity was present in a low molecular weight form of ~ 150 kDa.…”