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Biochemical, Molecular, and Genetic Mechanisms

Biotinylation of Histones Represses Transposable Elements in Human and Mouse Cells and Cell Lines and in Drosophila melanogaster^1–3,

⁴ Department of Nutrition and Health Sciences, University of Nebraska, Lincoln, NE 68583; ⁵ Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104; ⁶ Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, MO 63104; and ⁷ Department of Pediatrics and Human Genetics Laboratory, Munroe Meyer Institute for Genetics and Rehabilitation and ⁸ Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198

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.

^* To whom correspondence should be addressed. E-mail: jzempleni2{at}unl.edu.

Manuscript received 21 August 2008. Initial review completed 16 September 2008. Revision accepted 22 September 2008.

This article has been cited by other articles:

				J. Zempleni, Y. C. Chew, B. Bao, V. Pestinger, and S. S. K. Wijeratne Repression of Transposable Elements by Histone Biotinylation J. Nutr., December 1, 2009; 139(12): 2389 - 2392. [Abstract] [Full Text] [PDF]