Drosophila Genes in Development: Polycomb-group
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. Bithorax complex contains Pc-G response elements (PREs) that are involved in initiating and maintaining silencing of the whole bithorax complex (Busturia A., 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 F., 1994).
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 F., 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 A., 1992).
In laterstages the Polycomb-group (Pc-G) genes were found to keep homeotic genes stably repressed in those domains where they have to be inactive. At the molecular level the Pc-G is supposed to exert its repressory role by influencing the higher order structure of chromatin (Paro R. , 1993). 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.
Polycomb itself has a domain called the chromodomain, which is shared with HP1, a heterochromatin-associated protein of Drosophila (Paro R., 1991). Many of the Pc-G proteins, including Polycomb itself, are unable to bind DNA. 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 R., 1991 and Messmer S., 1992). Carboxy-terminal truncations of the PC protein do not affect chromosomal binding of PC. 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 S., 1992).
Pc protein is expressed in ovaries and during all stages of embryogenesis. Protein levels increase with developmental time in embryos. In the germline, most of the protein is found in the polyploid nurse cell nuclei. Some Pc protein is deposited in the oocyte but none is observed in the nucleus. A very dynamic pattern of expression involving overlapping gradients is observed in follicle cells during stages S10-S14. In embryos, Pc transcripts are homogenously distributed over the length of the embryo at the cellular blastoderm stage and in germ band extended embryos. In late stage embryos, transcripts are found predominantly in the CNS. Particularly strong expression is observed in the supra-, suboesophageal and anterior thoracic ganglia. Strong staining is also observed in the pharynx, salivary glands, and other internal tissues. (Paro R., 1993)
Pc protein and polyhomeotic protein have exactly the same binding patterns on polytene chromosomes. (Franke A., 1992)
Once established, the Polycomb group (Pc-G) and trithorax group (trx-G) gene products maintain the spatial pattern of Scr expression for the remainder of development. (Gindhart J. G., 1995).