Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Chromobox Protein Homolog 5
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Chromosomal Proteins, Non-Histone / metabolism*
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DNA-Binding Proteins / genetics
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Drosophila / genetics*
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Drosophila / metabolism*
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Drosophila Proteins*
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Eye Color / genetics
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Gene Rearrangement
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Genes, Insect
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Heterochromatin / genetics
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Histone-Lysine N-Methyltransferase
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Humans
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In Vitro Techniques
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Insect Proteins / genetics*
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Insect Proteins / metabolism*
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Leukemia, Myeloid, Acute / genetics
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Male
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Molecular Sequence Data
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Myeloid-Lymphoid Leukemia Protein
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Phenotype
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Proto-Oncogenes*
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Sequence Homology, Amino Acid
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Species Specificity
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Suppression, Genetic
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Transcription Factors / genetics*
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Transcription Factors / metabolism*
Substances
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Chromosomal Proteins, Non-Histone
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DNA-Binding Proteins
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Drosophila Proteins
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Heterochromatin
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Insect Proteins
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KMT2A protein, human
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MLLT10 protein, human
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Transcription Factors
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Trl protein, Drosophila
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Chromobox Protein Homolog 5
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Myeloid-Lymphoid Leukemia Protein
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Histone-Lysine N-Methyltransferase