Review
Polycomb group protein complexes: do different complexes regulate distinct target genes?

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Introduction

During embryogenesis, many different cell types are generated, organized in a variety of tissues and organs. The identities of these different cell types are characterized by distinct sets of active and inactive genes. The cell identities need to be maintained through cell division. To achieve this, the cell type specific expression patterns of active and inactive genes have to be stably transmitted to the daughter cells. It is believed that the establishment of the cell type specific gene expression patterns involves activation of gene expression at the level of promoters, enhancers and transcription factors. However, different levels of control mechanisms are required for the maintenance of cell type specific gene expression patterns through cell division. In all eukaryotes, several chromatin-associated protein complexes have been identified that are involved in the maintenance of cell type specificity, one of which is the polycomb group (PcG) complex.

PcG proteins have initially been identified in Drosophila as being involved in the maintenance of the correct expression patterns of homeotic genes. Homeotic genes are differentially expressed in specific embryonic body segments. As such, homeotic genes play a crucial role in the proper development and subsequent maintenance of the body plan, in both vertebrates and invertebrates. In PcG mutants, the expression patterns of homeotic genes are initiated normally, early in embryonic development [1], [2]. However, at later developmental stages, the homeotic genes become expressed in body segments where they normally remain repressed. This results in dramatic changes in the body plan, which are called homeotic transformations [3], [4], [5]. In PcG mutants, homeotic genes are expressed outside the body segments where they normally are repressed and this indicates that PcG proteins are involved in stable repression of homeotic genes. Similarly, a second class of proteins, named the trithorax (Trx) group (TrG), has been identified to counteract the action of the PcG proteins. In contrast with PcG proteins, TrG proteins are needed for stable expression of homeotic genes. Based on their respective modes of action, PcG and TrG proteins therefore represent a cellular memory system that is important for the heritable transmission of gene expression patterns.

PcG proteins have originally been identified in Drosophila, but in recent years, PcG homologs have also been found in other vertebrates and invertebrates, such as human, mouse, chicken, Xenopus and Caenorhabditis elegans (Table 1). In spite of the widespread existence of PcG proteins, very little is known about the underlying molecular mechanism by which PcG proteins silence genes. However, one important observation is that PcG proteins form large, chromatin-associated multimeric proteins complexes. It has, therefore, been suggested that PcG-mediated gene silencing is a result of interference with the chromatin structure of their target genes. Evidence is accumulating that PcG complexes differ considerably in their compositions and this has important consequences for the specificity by which they associate with target genes and ultimately, their biological functions. In this review, we will discuss (i) that different multimeric PcG protein complexes exist and that their compositions are cell type specific and developmentally regulated and (ii) that different PcG complexes associate with distinct target genes, which would explain that specific PcG genes have different biological functions.

Section snippets

Original suggestions for the existence of multimeric PcG protein complexes

In Drosophila, PcG genes have been defined as a class of up to 30 genes which have in common that, when mutated, similar phenotypes are induced. These phenotypes are all characterized by homeotic transformations [6], [7], [8], [9]. Most PcG mutants display only a weak phenotype and only a few mutants, such as the polycomb (Pc) mutant itself, display severe homeotic transformations [3]. However, when more than one PcG gene is mutated, the homeotic transformations are strongly enhanced. This has

Are there cell type specific PcG complexes with different protein compositions?

Above, we raised the possibility that PcG complexes may differ in composition at different developmental times. This is, for instance, obvious in the case of esc, which is only expressed during the very early development of Drosophila embryos [49]. At later developmental stages, the esc protein is therefore principally absent from the PcG complex. Below, we will review data indicating that the composition of PcG complexes may differ considerably.

A striking outcome from the several two-hybrid

PcG response elements (PREs)

At present, a number of PcG proteins have been identified and increasingly more is known about the interaction between the different PcG proteins and their capacity to form multimeric protein complexes. Much less is known about how these PcG complexes are associated to their target genes. PcG proteins are thought to be involved in the maintenance of the repressed state of target genes by inducing changes in the chromatin structure. For the propagation of an inactive chromatin state, cis-acting

Concluding remarks

PcG proteins form multimeric, chromatin-associated protein complexes that are involved in the transmission of the transcriptionally repressed status of genes through cell division. This process provides an important basis for stable cell differentiation. In this review, we have discussed genetic and biochemical evidence for the existence of vertebrate PcG complexes with different compositions. There are various ways to create diversity in PcG complexes. Firstly, there appear to be two distinct

Acknowledgements

We thank Roel van Driel and Richard Sewalt for critically reading of the manuscript.

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