Gene name - Polycomb
Cytological map position - 78C9
Function - transcription factor
Keywords - Polycomb group
Symbol - Pc
Genetic map position - 3-47.1
Classification - chromo domain
Cellular location - nuclear
What are the targets of Polycomb-group (Pc-G) proteins and how do they regulate gene silencing? Pc-G proteins are usually considered to be inhibitors of homeotic genes, since Pc-G mutants were originally identified on the basis of their causing expression of homeotic genes in unusual locations, areas in which they normally would not be expressed. This so-called ectopic expression is attributed to the failure of proper gene silencing in Pc-G mutants. In fact bithorax complex contains Pc-G response elements (PREs) that are involved in initiating and maintaining silencing of the whole bithorax complex (Busturia, 1993).
Pc-G genes also regulate gap genes giant and knirps, restructuring their transcription to the posterior half of the embryo. This silencing is inititated by high levels of Hunchback protein in the anterior portion of the embryo, and maintained by Pc-G action (Pelegri, 1994).
The action of Pc-G proteins is thought to be mediated through chromatin. Chromatin is a combination of DNA and protein that derives its name from a staining reaction with dyes. About a third of the DNA in chromosomes is held in heterochromatin, a type of chromatin with which few genes are associated. Placing active genes next to heterochromatin results in their inactivation or variation in expression, an effect termed position effect variation. It is thought that heterochromatin is capable of spreading to active genes, resulting in their silencing (Spofford, 1976).
These classic biological observations have taken on a new and more literal meaning recently with the discovery of common sequence domains in Pc-G genes. Polycomb itself has a domain called the chromodomain, which is shared with HP1, a heterochromatin-associated protein of Drosophila (Paro, 1991). Many of the Pc-G proteins, including Polycomb itself, are unable to bind DNA.
Considering that they lack the ability to bind DNA, how do Pc-G proteins function to establish gene silencing? It is thought that the initial repression of a gene is carried out by transcription factors that possess the ability to recognize DNA. In the cases of giant and knirps, for example, the maternal protein Hunchback represses their expression in the anterior part of the embryo (Pelegri, 1994). Pc-G proteins provide a mechanism whereby initial repression becomes permanent. They carry out this role by assembling at the site of initial repression and forming a multiprotein complex involved in modifying chromatin to promote gene silencing. Polycomb itself has this ability to self associate (Franke, 1992).
Thus many of the roles of Pc-G proteins are played out not in association with DNA but in association with each other and with other chromosomal proteins, especially histones, the principle scaffolding protein of chromosomes. Interest in the silencing of gene expression has shifted from a concern about DNA-protein interaction to an emphasis on protein-protein interaction, and the maintenance and modification of chromatin structure (Reviewed by Orlando, 1995, Pirrotta, 1995 and Simon, 1995).
Trithorax group (trx-G) genes are able to reverse the inactivating effects of chromatin. These proteins are thought to function as transcriptional activators, removing the block on gene expression put in place by arrays of inactivating proteins.
Bases in 5' UTR - 107
Exons - two - The intron is centered in the chromo domain (Paro, 1993).
Bases in 3' UTR - 1170
The PC protein exhibits homology to the heterochromatin associated protein HP1 (Platero, 1995). The homology is confined to a 37 amino acid domain in the N-terminal part of the two proteins. This region is termed the chromo domain, standing for chromatin organization modifier (Paro, 1991 and Messmer, 1992). Carboxy-terminal truncations of the PC protein do not affect chromosomal binding of PC. However, mutations affecting only the chromo domain (including in vitro generated deletions, as well as point mutations) abolish chromosomal binding. Thus the chromo domain is important for the function of PC and it is absolutely required for binding of PC protein to chromatin. Some of the nuclear patterns generated by the mutated forms of the fusion proteins suggest that the chromo domain could be involved in a packaging mechanism, essential for compacting chromosomal proteins within heterochromatin or heterochromatin-like complexes (Messmer, 1992).
date revised: 3 July 97
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