title: Radiation-induced alterations of histone post-translational modification levels in lymphoblastoid cell lines.
abstract: BACKGROUND
  Radiation-induced alterations in posttranslational histone modifications (PTMs) may affect the cellular response to radiation damage in the DNA. If not reverted appropriately, altered PTM patterns may cause long-term alterations in gene expression regulation and thus lead to cancer. It is therefore important to characterize radiation-induced alterations in PTM patterns and the factors affecting them.
  
  
  METHODS
  A lymphoblastoid cell line established from a normal donor was used to screen for alterations in methylation levels at H3K4, H3K9, H3K27, and H4K20, as well as acetylation at H3K9, H3K56, H4K5, and H4K16, by quantitative Western Blot analysis at 15 min, 1 h and 24 h after irradiation with 2 Gy and 10 Gy. The variability of alterations in acetylation marks was in addition investigated in a panel of lymphoblastoid cell lines with differing radiosensitivity established from lung cancer patients.
  
  
  RESULTS
  The screening procedure demonstrated consistent hypomethylation at H3K4me3 and hypoacetylation at all acetylation marks tested. In the panel of lymphoblastoid cell lines, however, a high degree of inter-individual variability became apparent. Radiosensitive cell lines showed more pronounced and longer lasting H4K16 hypoacetylation than radioresistant lines, which correlates with higher levels of residual γ-H2AX foci after 24 h.
  
  
  CONCLUSIONS
  So far, the factors affecting extent and duration of radiation-induced histone alterations are poorly defined. The present work hints at a high degree of inter-individual variability and a potential correlation of DNA damage repair capacity and alterations in PTM levels.
authors.forename: Belinda
authors.initials: B
authors.lastname: Maroschik
authors.forename: Anne
authors.initials: A
authors.lastname: Gürtler
authors.forename: Anne
authors.initials: A
authors.lastname: Krämer
authors.forename: Ute
authors.initials: U
authors.lastname: Rößler
authors.forename: Maria
authors.initials: M
authors.lastname: Gomolka
authors.forename: Sabine
authors.initials: S
authors.lastname: Hornhardt
authors.forename: Simone
authors.initials: S
authors.lastname: Mörtl
authors.affiliation: Department of Radiation Oncology, Ludwig-Maximilians-University, Munich, Germany. anna.friedl@lrz.uni-muenchen.de.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Friedl
mesh_terms: D000107:Acetylation; D002461:Cell Line, Transformed; D004249:DNA Damage; D005720:Gamma Rays; D005786:Gene Expression Regulation / Q000528:radiation effects; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D011499:Protein Processing, Post-Translational / Q000528:radiation effects*; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000235:genetics
chemical_list: D006657:Histones; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase