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Introduction

A key feature of development in metameric animals is the definition of body segments where groups of cells with a specified fate will give rise to their relative body structures. Cell fates are specified by particular combinations of homeotic gene products. During early embryogenesPRE_artworkis, maternal and segmentation genes regulate homeotic genes by binding to specific regulatory sequences located in the promoter regions.  Later in development, the expression pattern of homeotic genes as well as other important developmental genes are maintained by a cell memory system dependent on two groups of genes. The members of these two groups are epigenetic regulators able to recognize the active and inactive state of expression and fix it to the cell progeny through many cell divisions. These components have been classified in two genetic groups. The trithorax-group (trxG) can maintain the active state of expression, while the Polycomb-group (PcG) counteracts this activation with a stable repressive function (Figure).

There is strong evidence that the epigenetic memory established by these two groups of proteins is achieved through regulation of higher order chromatin structures, but the molecular mechanisms of this regulation are little understood, although insights on their molecular function have emerged in the last years. PcG gene products form large multimeric protein complexes in Drosophila, mouse and human. These complexes are able to induce specific histone modifications and to counteract the action of ATP-dependent chromatin remodelling complexes. PcG mediated gene silencing can be directed by DNA elements in cis, defined as PcG response elements (PREs). When PREs are placed upstream to reporter genes, they induce a PcG dependent repression of transcription with a characteristic mosaic-like pattern reminiscent of the phenomenon called "position effect variegation" (PEV), a transcriptional silencing of euchromatic genes by heterochromatin spreading into flanking sequences. On the other hand, several trxG members encode for proteins involved in histone modifications, that are distinct from those induced by the PcG, and in ATP-dependent chromatin remodeling, thereby increasing chromatin accessibility to transcription factors. PcG and trxG proteins act at regulatory elements that are often overlapping along the chromosome. This suggests that epigenetic information for the regulation of silencing and activation is localised at switchable DNA elements containing PREs and the sequence response elements for trxG genes (TREs). These joint PRE/TRE elements were also defined as Cellular Memory Modules (CMM)

We are currently interested in several aspects of PcG and trxG mediated gene regulation: i) the molecular analysis of the cellular memory function. ii) the effect of PcG and trxG proteins on the nuclear compartmentalisation of their target genes. iii) Genome-wide analysis of the action of PcG and trxG genes. More information on these subjects is available on the links below:
 
   

Molecular analysis
Nuclear architecture
Genome-wide analysis of PcG/trxG proteins


Last update: 22/08/2008