Document Detail


K12-biotinylated histone H4 is enriched in telomeric repeats from human lung IMR-90 fibroblasts.
MedLine Citation:
PMID:  19369050     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Subhashinee S K Wijeratne; Gabriela Camporeale; Janos Zempleni
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Validation Studies     Date:  2009-04-14
Journal Detail:
Title:  The Journal of nutritional biochemistry     Volume:  21     ISSN:  1873-4847     ISO Abbreviation:  J. Nutr. Biochem.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-15     Completed Date:  2010-06-14     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  9010081     Medline TA:  J Nutr Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  310-6     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Nutrition and Health Sciences, University of Nebraska at Lincoln, Lincoln, NE 68583-0806, USA.
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MeSH Terms
Descriptor/Qualifier:
Biological Markers / metabolism
Biotinylation
Carbon-Nitrogen Ligases / genetics,  metabolism
Cell Aging*
Cell Line
Cells, Cultured
Epigenesis, Genetic
Fibroblasts / metabolism
Gene Expression
Histones / metabolism*
Humans
Lung / metabolism
Lysine / metabolism*
Protein Processing, Post-Translational
RNA, Messenger / metabolism
Repetitive Sequences, Nucleic Acid*
Symporters / genetics,  metabolism
Telomerase / genetics,  metabolism
Telomere / metabolism*
Grant Support
ID/Acronym/Agency:
DK063945/DK/NIDDK NIH HHS; DK077816/DK/NIDDK NIH HHS; ES015206/ES/NIEHS NIH HHS; R01 DK063945-05A1/DK/NIDDK NIH HHS; R01 DK063945-06/DK/NIDDK NIH HHS; R01 DK077816-01A2/DK/NIDDK NIH HHS; R01 DK077816-01A2S1/DK/NIDDK NIH HHS; R01 DK077816-02/DK/NIDDK NIH HHS; R21 DK082476-01/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Histones; 0/RNA, Messenger; 0/Symporters; 0/biotin transporter; 56-87-1/Lysine; EC 2.7.7.49/Telomerase; EC 6.3.-/Carbon-Nitrogen Ligases; EC 6.3.4.-/holocarboxylase synthetases
Comments/Corrections

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