A view of nuclear Polycomb bodies

Abstract

Polycomb group (PcG) proteins are concentrated in nuclear foci called PcG bodies. Although some of these foci are due to the tendency of PcG binding sites in the genome to occur in linear clusters, distant PcG sites can contact one another and in some cases congregate in the same PcG body when they are repressed. Experiments using transgenes containing PcG binding sites reveal that co-localization depends on the presence of insulator elements rather than of Polycomb Response Elements (PREs) and that it can occur also when the transgenes are in the active state. A model is proposed according to which insulator proteins mediate shuttling of PcG target genes between PcG bodies when repressed to transcription factories when transcriptionally active.

Figure 1. Polycomb bodies

(a) Human embryonic stem cell line stained with antibody against the PcG protein Ring1B (reproduced from ref. , with permission). (b) Polycomb bodies visualized in the human cancer cell line U2OS expressing GFP-BMI1 (reproduced from ref. , with permission). (c) Drosophila live imaginal disc cells expressing GFP-PH (reproduced from Development, ref. , with permission). (d) HeLa cell nucleus stained with anti-CTCF (red) and anti-PC2/CBX4 (green). The two images are merged to show remarkable co-localization (reproduced from ref. , with permission).

Figure 2. Constitutive bodies and dynamic bodies

(a) Hilbert folding representation of Polycomb binding sites on chromosome 3R of Drosophila. Some 75-100 (depending on how they are counted) PC binding sites correspond to this map that shows a high degree of clustering along the chromosome. The diagrams on the left explain how the iterative Hilbert folding (for two dimensions, called Peano folding; for applications to genomic data see ref. 51) of the linear chromosome arm is achieved. Figure kindly provided by P. Kharchenko. (b) The Drosophila Antp gene (magenta) and the Abd-B gene (red) visualized by FISH co-localize within a PcG body (Polycomb) in nuclei from the embryonic head region, where both are repressed by PcG complexes. In nuclei from the posterior region, the active Antp gene moves out of the PcG body but the repressed Abd-B gene remains associated with the PcG body (reproduced from ref. , with permission)

Figure 3. A shuttling model for the assembly of PcG target genes into nuclear bodies

A generalized PcG target gene is presumed to be associated with one or more of each Enhancer, PRE, and Insulator elements. In this speculative model the insulator drives the association of such PcG target genes into PcG bodies when they are repressed. When the gene switches to the transcriptionally active state, it generally forms a domain that binds N-ter Trithorax and ASH1 proteins [33]. The insulator now targets the active gene to a Trithorax transcription factory. The switch in insulator preference for transcription factory vs PcG body localization might depend on modifications such as, for example, acetylation vs sumoylation.