Reversible disruption of pericentric heterochromatin and centromere function by inhibiting deacetylases.
Histone modifications might act to mark and maintain functional chromatin domains during both interphase and mitosis. Here we show that pericentric heterochromatin in mammalian cells is specifically responsive to prolonged treatment with deacetylase inhibitors. These defined regions relocate at the nuclear periphery and lose their properties of retaining HP1 (heterochromatin protein 1) proteins. Subsequent defects in chromosome segregation arise in mitosis. All these changes can reverse rapidly after drug removal. Our data point to a crucial role of histone underacetylation within pericentric heterochromatin regions for their association with HP1 proteins, their nuclear compartmentalization and their contribution to centromere function.
Taddei
A
A
Institut Curie/Research section, UMR 218 du CNRS, 26 rue d'Ulm, 75248 Paris cedex 05, France.
Maison
C
C
Roche
D
D
Almouzni
G
G
D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002503:Centromere / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006570:Heterochromatin / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D018613:Microscopy, Confocal; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism
D004791:Enzyme Inhibitors; D006570:Heterochromatin; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D011994:Recombinant Proteins; C012589:trichostatin A; D004247:DNA; D006655:Histone Deacetylases