K12-biotinylated histone H4 is enriched in telomeric repeats from human lung IMR-90 fibroblasts.
Covalent modifications of histones play a role in regulating telomere attrition and cellular senescence. Biotinylation of lysine (K) residues in histones, mediated by holocarboxylase synthetase (HCS), is a novel diet-dependent mechanism to regulate chromatin structure and gene expression. We have previously shown that biotinylation of K12 in histone H4 (H4K12bio) is a marker for heterochromatin and is enriched in pericentromeric alpha satellite repeats. Here, we hypothesized that H4K12bio is also enriched in telomeres. We used human IMR-90 lung fibroblasts and immortalized IMR-90 cells overexpressing human telomerase (hTERT) in order to examine histone biotinylation in young and senescent cells. Our studies suggest that one out of three histone H4 molecules in telomeres is biotinylated at K12 in hTERT cells. The abundance of H4K12bio in telomeres decreased by 42% during telomere attrition in senescent IMR-90 cells; overexpression of telomerase prevented the loss of H4K12bio. Possible confounders such as decreased expression of HCS and biotin transporters were formally excluded in this study. Collectively, these data suggest that H4K12bio is enriched in telomeric repeats and represents a novel epigenetic mark for cell senescence.
Department of Nutrition and Health Sciences, University of Nebraska at Lincoln, Lincoln, NE 68583-0806, USA.
Subhashinee S K
SS
Wijeratne
Gabriela
G
Camporeale
Janos
J
Zempleni
D015415:Biomarkers / Q000378:metabolism; D019921:Biotinylation; D019731:Carbon-Nitrogen Ligases / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D016922:Cellular Senescence; D044127:Epigenesis, Genetic; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000378:metabolism; D008239:Lysine / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*
D015415:Biomarkers; D006657:Histones; D012333:RNA, Messenger; D027981:Symporters; C119981:biotin transporter; D019098:Telomerase; D019731:Carbon-Nitrogen Ligases; C023312:holocarboxylase synthetases; D008239:Lysine