Biotinylation of histones represses transposable elements in human and mouse cells and cell lines and in Drosophila melanogaster

Ching Chew Yap, John T. West, Stephanie J. Kratzer, Anne M. Ilvarsonn, Joel C. Eissenberg, Bhavana J. Dave, David Klinkebiel, Judith K. Christman, Janos Zempleni

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Transposable elements such as long terminal repeats (LTR) constitute ∼45% of the human genome; transposition events impair genome stability. Fifty-four promoter-active retrotransposons have been identified in humans. Epigenetic mechanisms are important for transcriptional repression of retrotransposons, preventing transposition events, and abnormal regulation of genes. Here, we demonstrate that the covalent binding of the vitamin biotin to lysine-12 in histone H4 (H4K12bio) and lysine-9 in histone H2A (H2AK9bio), mediated by holocarboxylase synthetase (HCS), is an epigenetic mechanism to repress retrotransposon transcription in human and mouse cell lines and in primary cells from a human supplementation study. Abundance of H4K12bio and H2AK9bio at intact retrotransposons and a solitary LTR depended on biotin supply and HCS activity and was inversely linked with the abundance of LTR transcripts. Knockdown of HCS in Drosophila melanogaster enhances retrotransposition in the germline. Importantly, we demonstrated that depletion of H4K12bio and H2AK9bio in biotin-deficient cells correlates with increased production of viral particles and transposition events and ultimately decreases chromosomal stability. Collectively, this study reveals a novel diet-dependent epigenetic mechanism that could affect cancer risk.

Original languageEnglish (US)
Pages (from-to)2316-2322
Number of pages7
JournalJournal of Nutrition
Volume138
Issue number12
DOIs
StatePublished - Dec 2008

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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