HISTONE DEACETYLASE - A KEY ENZYME FOR THE BINDING OF REGULATORY PROTEINS TO CHROMATIN

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.