title: The C-terminal SET domains of ALL-1 and TRITHORAX interact with the INI1 and SNR1 proteins, components of the SWI/SNF complex.
abstract: The ALL-1 gene was discovered by virtue of its involvement in human acute leukemia. Its Drosophila homolog trithorax (trx) is a member of the 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 screening of Drosophila cDNA library and detected interaction between a TRX polypeptide spanning SET and the SNR1 protein. SNR1 is a product of snr1, which is classified as a trx group gene. We found parallel interaction in yeast between the SET domain of ALL-1 and the human homolog of SNR1, INI1 (hSNF5). These results were confirmed by in vitro binding studies and by demonstrating coimmunoprecipitation of the proteins from cultured cells and/or transgenic flies. Epitope-tagged SNR1 was detected at discrete sites on larval salivary gland polytene chromosomes, and these sites colocalized with around one-half of TRX binding sites. Because SNR1 and INI1 are constituents of the SWI/SNF complex, which acts to remodel chromatin and consequently to activate transcription, the interactions we observed suggest a mechanism by which the SWI/SNF complex is recruited to ALL-1/trx targets through physical interactions between the C-terminal domains of ALL-1 and TRX and INI1/SNR1.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: O
authors.initials: O
authors.lastname: Rozenblatt-Rosen
authors.forename: T
authors.initials: T
authors.lastname: Rozovskaia
authors.forename: D
authors.initials: D
authors.lastname: Burakov
authors.forename: Y
authors.initials: Y
authors.lastname: Sedkov
authors.forename: S
authors.initials: S
authors.lastname: Tillib
authors.forename: J
authors.initials: J
authors.lastname: Blechman
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: C M
authors.initials: CM
authors.lastname: Croce
authors.forename: A
authors.initials: A
authors.lastname: Mazo
authors.forename: E
authors.initials: E
authors.lastname: Canaani
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D005075:Biological Evolution; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007938:Leukemia; D051788:Myeloid-Lymphoid Leukemia Protein; D011519:Proto-Oncogenes; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C497422:KMT2A protein, human; D011994:Recombinant Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; C096659:Snr1 protein, Drosophila; D014157:Transcription Factors; C063460:Trl protein, Drosophila; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase