Homo-oligomerisation and nuclear localisation of mouse histone deacetylase1

Reversible histone acetylation changes the chromatin structure and can modu late gene transcription. Mammalian histone deacetylase 1 (HDAC1) is a nucle ar protein that belongs to a growing family of evolutionarily conserved enz ymes catalysing the removal of acetyl residues from core histones and other proteins. Previously, we have identified murine HDAC1 as a growth factor-i nducible protein in murine T-cells. Here, we characterise the molecular fun ction of mouse HDAC1 in more detail. immunoprecipitation experiments with e pitope-tagged HDAC1 protein reveal the association with endogenous HDAC1 en zyme. We show that HDAC1 can homo-oligomerise and that this interaction is dependent on the N-terminal HDAC association domain of the protein. Further more, the same HDAC1 domain is also necessary for in vitro binding of HDAC2 and HDAC3, association with RbAp48 and for catalytic activity of the enzym e. A lysine-rich sequence within the carboxy terminus of HDAC1 is crucial for nuclear localisation of the enzyme. We identify a C-terminal nuclear locali sation domain, which is sufficient for the transport of HDAC1 and of report er fusion proteins into the nucleus. Alternatively, HDAC1 can be shuttled i nto the nucleus by association with another HDAC1 molecule via its N-termin al HDAC association domain. Our results define two domains, which are essen tial for the oligomerisation and nuclear localisation of mouse HDAC1. (C) 2 001 Academic Press.