title: Formaldehyde-induced histone modifications in vitro.
abstract: Numerous experiments have demonstrated the genotoxic and mutagenic effects of formaldehyde, including DNA-protein cross-links (DPC). Histone was reported to be involved in the formation of DPC in which the epsilon-amino groups of lysine and exocyclic amino groups of DNA were thought to be cross-linked through multiple step reactions. Using mass spectrometry, the N-terminus of histone and lysine residues located in both the histone N-terminal tail and the globular fold domain were identified as binding sites for formaldehyde in the current study. The observation that only lysine residues without post-translational modification (PTM) can be attacked by formaldehyde indicates that PTM blocks the reaction between lysine and formaldehyde. Additionally, we found that formaldehyde-induced Schiff bases on lysine residues could inhibit the formation of PTM on histone, raising the possibility that formaldehyde might alter epigenetic regulation.
authors.affiliation: Curriculum in Applied Science & Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Kun
authors.initials: K
authors.lastname: Lu
authors.forename: Gunnar
authors.initials: G
authors.lastname: Boysen
authors.forename: Lina
authors.initials: L
authors.lastname: Gao
authors.forename: Leonard B
authors.initials: LB
authors.lastname: Collins
authors.forename: James A
authors.initials: JA
authors.lastname: Swenberg
mesh_terms: D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D005557:Formaldehyde / Q000737:chemistry* / Q000378:metabolism; D006657:Histones / Q000737:chemistry* / Q000378:metabolism; D066298:In Vitro Techniques; D008239:Lysine / Q000737:chemistry / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry; D010449:Peptide Mapping; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D003432:Cross-Linking Reagents; D006657:Histones; D010446:Peptide Fragments; D005557:Formaldehyde; D004247:DNA; D008239:Lysine