Epigenetic Regulation: Another Layer to Hedgehog Signaling

Abstract

In Drosophila , the trithorax-group (trxG) and polycomb-group (PcG) proteins maintain chromatin in active or silenced states, respectively, to allow the maintenance of a genetic program of cellular identity. This process has been called "cellular memory" and the epigenetically marked DNA has been called a "cellular memory module." Thus far, the PcG and trxG proteins have been understood to regulate the expression of homeotic genes. Maurange and Paro provide evidence from chromatin immunoprecipitation experiments that the gene encoding the morphogen hedgehog (hh) contains two PcG response elements (PRE) and binds members of the PcG and trxG complexes, specifically Polycomb and GAGA factor (GAF). Insertion of an upstream activating sequence (UAS) into a promoter allows the GAL4 transcription factor to stimulate gene expression. When the UAS was placed in proximity to the hh PRE, expression of hh by GAL4 was suppressed. GAL4 stimulated expression in flies genetically compromised for PcG function. When engrailed (EN), which stimulates hh expression, was activated inappropriately in a two-cell-wide strip at the dorsal-ventral boundary, hh expression persisted in the daughter cells later in wing development despite loss of expression of en . When the same artificial system driving en expression was used in a dorsal-ventral strip, the requirement for the PgC and trxG proteins for the inheritance of hh expression was confirmed using flies with genetic mutations affecting either PcG or trxG activity. These results expand the role for the trxG and PcG complexes to later stages of development and tissue patterning and provide an additional mechanism controlling morphogenic signaling. C. Maurange, R. Paro, A cellular memory module conveys epigenetic inheritance of hedgehog expression during Drosophila wing imaginal disc development. Genes Dev. 16 , 2672-2683 (2002). [Abstract] [Full Text]