Abstract
Heterochromatin integrity is crucial for genome stability and regulation of gene expression, but the factors involved in mammalian heterochromatin biology are only incompletely understood. Here we identify the oncoprotein DEK, an abundant nuclear protein with a previously enigmatic in vivo function, as a Suppressor of Variegation [Su(var)] that is crucial to global heterochromatin integrity. We show that DEK interacts directly with Heterochromatin Protein 1 α (HP1α) and markedly enhances its binding to trimethylated H3K9 (H3K9me3), which is key for maintaining heterochromatic regions. Loss of Dek in Drosophila leads to a Su(var) phenotype and global reduction in heterochromatin. Thus, these findings show that DEK is a key factor in maintaining the balance between heterochromatin and euchromatin in vivo.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Cell Cycle / drug effects
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Chromobox Protein Homolog 5
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Chromosomal Proteins, Non-Histone / genetics
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Chromosomal Proteins, Non-Histone / metabolism*
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism
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Gene Expression Regulation
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Gene Knockdown Techniques
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Genomic Instability / genetics
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HEK293 Cells
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HeLa Cells
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Heterochromatin / genetics*
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Heterochromatin / metabolism*
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Histone Deacetylase Inhibitors / pharmacology
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Histones / metabolism
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Humans
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Microscopy, Electron, Transmission
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Oncogene Proteins / genetics
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Oncogene Proteins / metabolism*
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Poly-ADP-Ribose Binding Proteins
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Protein Binding
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Receptors, Eph Family / genetics
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Receptors, Eph Family / metabolism
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Tumor Cells, Cultured
Substances
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CBX5 protein, human
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Chromosomal Proteins, Non-Histone
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DEK protein, human
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Drosophila Proteins
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Heterochromatin
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Histone Deacetylase Inhibitors
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Histones
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Oncogene Proteins
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Poly-ADP-Ribose Binding Proteins
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Chromobox Protein Homolog 5
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Dek protein, Drosophila
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Receptors, Eph Family