title: Epigenetic aspects of HP1 exchange kinetics in apoptotic chromatin.
abstract: Apoptotic bodies are the most condensed form of chromatin. In general, chromatin structure and function are mostly dictated by histone post-translational modifications. Thus, we have analyzed the histone signature in apoptotic cells, characterized by pronounced chromatin condensation. Here, H2B mono-acetylation, and H3K9 and H4 acetylation was significantly decreased in apoptotic cells, which maintained a high level of H3K9 methylation. This phenotype was independent of p53 function and distinct levels of anti-apoptotic Bcl2 protein. Interestingly, after etoposide treatment of leukemia and multiple myeloma cells, H3K9 and H4 hypoacetylation was accompanied by increased H3K9me2, but not H3K9me1 or H3K9me3. In adherent mouse fibroblasts, a high level of H3K9me3 and histone deacetylation in apoptotic bodies was likely responsible for the pronounced (∼40%) recovery of GFP-HP1α and GFP-HP1β after photobleaching. HP1 mobility in apoptotic cells appeared to be unique because limited exchange after photobleaching was observed for other epigenetically important proteins, including GFP-JMJD2b histone demethylase (∼10% fluorescence recovery) or Polycomb group-related GFP-BMI1 protein (∼20% fluorescence recovery). These findings imply a novel fact that only certain subset of proteins in apoptotic bodies is dynamic.
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Královopolská 135, 612 65 Brno, Czech Republic.
authors.forename: Soňa
authors.initials: S
authors.lastname: Legartová
authors.forename: Alžběta
authors.initials: A
authors.lastname: Jugová
authors.forename: Lenka
authors.initials: L
authors.lastname: Stixová
authors.forename: Stanislav
authors.initials: S
authors.lastname: Kozubek
authors.forename: Miloslava
authors.initials: M
authors.lastname: Fojtová
authors.forename: Zbyněk
authors.initials: Z
authors.lastname: Zdráhal
authors.forename: Gabriela
authors.initials: G
authors.lastname: Lochmanová
authors.forename: Eva
authors.initials: E
authors.lastname: Bártová
mesh_terms: D000107:Acetylation; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic; D017209:Apoptosis / Q000187:drug effects*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002843:Chromatin / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005047:Etoposide; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008745:Methylation; D051379:Mice; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C000715593:CBX1 protein, human; C000715594:CBX5 protein, human; C096188:Cbx1 protein, mouse; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D000090266:Chromobox Protein Homolog 5; D005047:Etoposide