title: Biotinylation is a natural, albeit rare, modification of human histones.
abstract: Previous studies suggest that histones H3 and H4 are posttranslationally modified by binding of the vitamin biotin, catalyzed by holocarboxylase synthetase (HCS). Albeit a rare epigenetic mark, biotinylated histones were repeatedly shown to be enriched in repeat regions and repressed loci, participating in the maintenance of genome stability and gene regulation. Recently, a team of investigators failed to detect biotinylated histones and proposed that biotinylation is not a natural modification of histones, but rather an assay artifact. Here, we describe the results of experiments, including the comparison of various analytical protocols, antibodies, cell lines, classes of histones, and radiotracers. These studies provide unambiguous evidence that biotinylation is a natural, albeit rare, histone modification. Less than 0.001% of human histones H3 and H4 are biotinylated, raising concerns that the abundance might too low to elicit biological effects in vivo. We integrated information from this study, previous studies, and ongoing research efforts to present a new working model in which biological effects are caused by a role of HCS in multiprotein complexes in chromatin. In this model, docking of HCS in chromatin causes the occasional binding of biotin to histones as a tracer for HCS binding sites.
authors.affiliation: Department of Nutrition and Health Sciences, University of Nebraska at Lincoln, Lincoln, NE 68583-0806, USA.
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Kuroishi
authors.forename: Luisa
authors.initials: L
authors.lastname: Rios-Avila
authors.forename: Valerie
authors.initials: V
authors.lastname: Pestinger
authors.forename: Subhashinee S K
authors.initials: SS
authors.lastname: Wijeratne
authors.forename: Janos
authors.initials: J
authors.lastname: Zempleni
mesh_terms: D000906:Antibodies / Q000737:chemistry; D000918:Antibody Specificity; D000941:Antigens / Q000737:chemistry / Q000276:immunology; D001710:Biotin / Q000378:metabolism; D019921:Biotinylation; D015153:Blotting, Western; D002457:Cell Extracts / Q000737:chemistry; D045744:Cell Line, Tumor; D006657:Histones / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007106:Immune Sera / Q000737:chemistry; D019169:Jurkat Cells; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D019809:Streptavidin / Q000737:chemistry
chemical_list: D000906:Antibodies; D000941:Antigens; D002457:Cell Extracts; D006657:Histones; D007106:Immune Sera; D010446:Peptide Fragments; D001710:Biotin; D019809:Streptavidin