THE C-TERMINAL SET DOMAINS OF ALL-1 AND TRITHORAX INTERACT WITH THE INI1 AND SNR1 PROTEINS, COMPONENTS OF THE SWI SNF COMPLEX/

The ALL-1 gene was discovered by virtue of its involvement in human ac ute leukemia. Its Drosophila homolog trithorax (trx) is a member of th e trx-Polycomb gene family, which maintains correct spatial expression of the Antennapedia and bithorax complexes during embryogenesis, The C-terminal SET domain of ALL-1 and TRITHORAX (TRX) is a 150-aa motif, highly conserved during evolution. We performed yeast two hybrid scree ning of Drosophila cDNA library and detected interaction between a TRY poly-peptide spanning SET and the SNR1 protein. SNR1 is a product of snr1, which is classified as a trx group gene. We found parallel inter action in yeast between the SET domain of ALL-1 and the human homolog of SNR1, INI1 (hSNF5). These results were confirmed by in vitro bindin g studies and by demonstrating coimmunoprecipitation of the proteins f rom cultured cells and/or transgenic flies. Epitope-tagged SNRI was de tected at discrete sites on larval salivary gland polytene chromosomes , and these sites colocalized with around one-half of TRX binding site s. Because SNR1 and INI1 are constituents of the SWI/SNF complex, whic h acts to remodel chromatin and consequently to activate transcription , the interactions we observed suggest a mechanism by which the SWI/SN F complex is recruited to ALL-1/trx targets through physical interacti ons between the C-terminal domains of ALL-1 and TRX and INI1/SNR1.