THE HUMAN POLYCOMB GROUP COMPLEX ASSOCIATES WITH PERICENTROMERIC HETEROCHROMATIN TO FORM A NOVEL NUCLEAR DOMAIN

The Polycomb group (PcG) complex is a chromatin-associated multiprotei n complex, involved in the stable repression of homeotic gene activity in Drosophila. Recently, a mammalian PcG complex has been identified with several PcG proteins implicated in the regulation of Hox gene exp ression. Although the mammalian PcG complex appears analogous to the c omplex in Drosophila, the molecular mechanisms and functions for the m ammalian PcG complex remain unknown. Here we describe a detailed chara cterization of the human PcG complex in terms of cellular localization and chromosomal association. By using antibodies that specifically re cognize three human PcG proteins-RING1, BMI1, and hPc2-we demonstrate in a number of human cell lines that the PcG complex forms a unique di screte nuclear structure that we term PcG bodies. PcG bodies are promi nent novel nuclear structures with the larger PcG foci generally local ized near the centromeres, as visualized with a kinetochore antibody m arker. In both normal fetal and adult fibroblasts, PcG bodies are not randomly dispersed, but appear clustered into defined areas within the nucleus. We show in three different human cell lines that the PcG com plex can tightly associate with large pericentromeric heterochromatin regions (1q12) on chromosome 1, and with related pericentromeric seque nces on different chromosomes, providing evidence for a mammalian PcG- heterochromatin association. Furthermore, these heterochromatin-bound PcG complexes remain stably associated throughout mitosis, thereby all owing the potential inheritance of the PcG complex through successive cell divisions. We discuss these results in terms of the known functio n of the PcG complex as a transcriptional repression complex.