Histone deacetylase interacts directly with DNA topoisomerase II

Histone deacetylases (HDACs) modify nucleosomal histones, have a key role i n the regulation of gene transcription(1,2), and may be involved in cell-cy cle regulation, differentiation and human cancer(3,4). Purified recombinant human HDAC1 protein was used to screen a cDNA expression library, and one of the clones identified encoded DNA topoisomerase II (Topo II), an enzyme known to have a role in transcriptional regulation and chromatin organizati on(5,6). Coimmunoprecipitation experiments indicate that HDAC1 and HDAC2 ar e associated with Topo II in vivo under normal physiological conditions. Co mplexes containing Topo II possess HDAC activities, and complexes containin g HDAC1 or HDAC2 possess Topo II activities. HDAC and Topo II modify each o ther's activity in vitro and in vivo. Our results indicate the existence of a functionally coupled complex between these two enzymes and offer insight s into the potential mechanisms of action of both enzymes.