The GAGA factor of Drosophila interacts with SAP18, a Sin3-associated polypeptide

SAP18, a polypeptide associated with the Sin3-HDAC corepressor complex, was identified in a yeast two-hybrid screen as capable of interacting with the Drosophila GAGA factor. The interaction was confirmed in vitro by glutathi one S-transferase pull-down assays using recombinant proteins and crude SL2 nuclear extracts. The first 245 residues of GAGA, including the POZ domain , are necessary and sufficient to bind dSAP18. In polytene chromosomes, dSA P18 and GAGA co-localize at a few discrete sites and, in particular, at the bithorax complex where GAGA binds some silenced polycomb response elements . When the dSAP18 dose is reduced, flies heterozygous for the GAGA mutation Trl(67) show the homeotic transformation of segment A6 into A5, indicating that GAGA-dSAP18 interaction contributes to the functional regulation of t he iab-6 element of the bithorax complex. These results suggest that, throu gh recruitment of the Sin3-HDAC complex, GAGA might contribute to the regul ation of homeotic gene expression.