Biotinylation is a natural, albeit rare, modification of human histones

Toshinobu Kuroishi, Luisa Rios-Avila, Valerie Pestinger, Subhashinee S K Wijeratne, Janos Zempleni

Research output: Contribution to journalArticle

41 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)537-545
Number of pages9
JournalMolecular Genetics and Metabolism
Volume104
Issue number4
DOIs
StatePublished - Dec 1 2011

Fingerprint

Histone Code
Biotinylation
Histones
Chromatin
Multiprotein Complexes
Genomic Instability
Biotin
Epigenomics
Vitamins
Artifacts
Binding Sites
Maintenance
Research Personnel
Gene expression
Cell Line
Assays
holocarboxylase synthetases
Antibodies

Keywords

  • Biotin
  • Histones
  • Holocarboxylase synthetase
  • Post-translational modifications

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Cite this

Biotinylation is a natural, albeit rare, modification of human histones. / Kuroishi, Toshinobu; Rios-Avila, Luisa; Pestinger, Valerie; Wijeratne, Subhashinee S K; Zempleni, Janos.

In: Molecular Genetics and Metabolism, Vol. 104, No. 4, 01.12.2011, p. 537-545.

Research output: Contribution to journalArticle

Kuroishi, Toshinobu ; Rios-Avila, Luisa ; Pestinger, Valerie ; Wijeratne, Subhashinee S K ; Zempleni, Janos. / Biotinylation is a natural, albeit rare, modification of human histones. In: Molecular Genetics and Metabolism. 2011 ; Vol. 104, No. 4. pp. 537-545.
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