INTERACTION OF SP100 WITH HP1 PROTEINS - A LINK BETWEEN THE PROMYELOCYTIC LEUKEMIA-ASSOCIATED NUCLEAR-BODIES AND THE CHROMATIN COMPARTMENT

The PML/SP100 nuclear bodies (NBs) were first described as discrete su bnuclear structures containing the SP100 protein. Subsequently, they w ere shown to contain the PML protein which is part of the oncogenic PM L-RAR alpha hybrid produced by the t(15;17) chromosomal translocation characteristic of acute promyelocytic leukemia. Yet, the physiological role of these nuclear bodies remains unknown. Here, we show that SP10 0 binds to members of the heterochromatin protein 1 (HP1) families of non-histone chromosomal proteins. Further, we demonstrate that a natur ally occurring splice variant of SP100! here called SP100-HMG, is a me mber of the high mobility group-1 (HMG-1) protein family and may thus possess DNA-binding potential, Both HP1 and SP100-HMG concentrate in t he PML/SP100 NBs, and overexpression of SP100 leads to enhanced accumu lation of endogenous HP1 in these structures. When bound to a promoter , SP100, SP100-HMG and HP1 behave as transcriptional repressors in tra nsfected mammalian cells. These observations present molecular evidenc e for an association between the PML/SP100 NBs and the chromatin nucle ar compartment. They support a model in which the NBs may play a role in certain aspects of chromatin dynamics.