The Drosophila homolog of the human AF10 is an HP1-interacting suppressor of position effect variegation.
In chromosomal rearrangements of acute myeloid leukaemia patients the mixed lineage leukaemia (MLL) gene, a human homolog of the Drosophila gene trithorax, is frequently fused to AF10. Here we describe the identification and a functional characterization of the Drosophila homolog dAF10. We show that dAF10 functions in heterochromatin-dependent genomic silencing of position effect variegation, a phenomenon associated with chromosomal rearrangements that cause mosaic expression of euchromatic genes when relocated next to heterochromatin. We also demonstrate that dAF10 can associate with the heterochromatin protein 1 (HP1) in vitro and in vivo. The results indicate that dAF10 is an HP1-interacting component of the heterochromatin-dependent gene silencing pathway, which either contributes to the stability of the heterochromatin complex or to its function.
Linder
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Max-Planck-Institut für Biophysikalische Chemie, Abteilung Molekulare Entwicklungsbiologie, Am Fassberg 11, 37077 Göttingen, Germany.
Gerlach
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Jäckle
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H
D000595:Amino Acid Sequence; D000818:Animals; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins; D005127:Eye Color / Q000235:genetics; D015321:Gene Rearrangement; D017344:Genes, Insect; D006570:Heterochromatin / Q000235:genetics; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D066298:In Vitro Techniques; D019476:Insect Proteins / Q000235:genetics* / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein; D010641:Phenotype; D011519:Proto-Oncogenes; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013489:Suppression, Genetic; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006570:Heterochromatin; D019476:Insect Proteins; C497422:KMT2A protein, human; C092513:MLLT10 protein, human; D014157:Transcription Factors; C063460:Trl protein, Drosophila; D000090266:Chromobox Protein Homolog 5; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase