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Implications for 4‐Oxo‐2‐nonenal‐Derived Histone Adducts in Mediating Gene Expression
Author(s) -
Camarillo Jeannie Marie,
Galligan James J,
Marnett Lawrence J
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1053.4
Subject(s) - histone , acetylation , chromatin , chromatin remodeling , chromatin immunoprecipitation , histone code , gene expression , regulation of gene expression , microbiology and biotechnology , chemistry , biology , gene , biochemistry , nucleosome , promoter
Histone modifications play a critical role in the maintenance of chromatin structure and the regulation of gene expression. For example, Lys acetylation to histone tails results in chromatin remodeling to allow transcriptional activation of targeted genes. Recent work has identified core histones as targets for adduction by the oxidative stress‐derived lipid electrophile, 4‐oxo‐2‐nonenal (4‐ONE). Here, we investigate the potential implications of these modifications on gene expression. Using an alkyne analog of 4‐ONE, a 4‐ONE, we employed click chemistry to selectively tag modified proteins from RKO cells treated with electrophile. Our data reveal that a 4‐ONE is a long‐lived histone modification, present up to 24 hours after treatment. Using pharmacological inhibitors of histone acetylation and deacetylation, we observe alterations in the acetylation of core histones when cells are co‐treated with a 4‐ONE. These data suggest that a 4‐ONE modifications occur at physiologically relevant sites that regulate chromatin structure and gene expression. Further, utilizing a combination of chromatin immunoprecipitation and click chemistry, we can selectively pull out DNA associated with adducted histones, further suggesting a putative role for these modifications in the regulation of gene expression. Together, our data suggest that histone adducts may play a role in chromatin structure and the mediation of gene expression. Support or Funding Information NCI F31 CA192861 (JMC) and NCI R37 CA087819 (LJM)